Rodrigo Borgia studied law at Bologna where he graduated, not simply as Doctor of Law, but as "the most eminent and judicious jurisprudent." After the election of his uncle as Pope Calixtus III, he was ordained deacon and created Cardinal - Deacon of San Nicola in Carcere at the age of twenty - five in 1456, and the following year he was appointed vice - chancellor of the Holy Roman Church, nepotistic appointments characteristic of the age. In 1468 he was ordained to the priesthood and in 1471 he was consecrated bishop and appointed Cardinal - Bishop of Albano. Having served in the Roman Curia under five popes, Pius II, Paul II, Sixtus IV and Innocent VIII, Rodrigo Borgia acquired considerable administrative experience, influence and wealth.

On the death of Pope Innocent VIII on 25 July 1492, the three likely candidates for the Papacy were cardinals Borgia, Ascanio Sforza and Giuliano della Rovere. It was rumored but not substantiated that Borgia succeeded in buying the largest number of votes and Sforza, in particular, was bribed with four mule loads of silver. The benefices and offices granted Sforza, moreover, would be worth considerably more than four mule loads of silver. John Burchard, the conclave's master of ceremonies and a leading figure of the papal household under several popes, recorded in his diary that the 1492 conclave was a particularly expensive campaign. Della Rovere was bankrolled to the cost of 200,000 gold ducats by King Charles VIII of France, with another 100,000 supplied by the Republic of Genoa. Borgia was elected on 11 August 1492, assuming the name of Alexander VI (due to confusion about the status of Pope Alexander V elected by the Council of Pisa). Giovanni di Lorenzo de' Medici (later Pope Leo X) is rumored to have sharply criticized the election and issued a warning:

Now we are in the power of a wolf, the most rapacious perhaps that this world has ever seen. And if we do not flee, he will inevitably devour us all.

Such a criticism however, particularly by the very youthful Giovanni, is believed highly unlikely: "Precocious though be was, the cardinal would scarcely have made this observation when sixteen years of age."

In contrast to the preceding pontificate, Pope Alexander VI adhered initially to strict administration of justice and orderly government. Before long, however, he began endowing his relatives at the church's and his neighbors' expense. Cesare Borgia his son, while a youth of seventeen and a student at Pisa, was made Archbishop of Valencia, and Giovanni Borgia inherited the Spanish Dukedom of Gandia, the Borgias' ancestral home in Spain. For the Duke of Gandia and for Gioffre, also known as Goffredo, the Pope proposed to carve fiefs out of the papal states and the Kingdom of Naples. Among the fiefs destined for the duke of Gandia were Cerveteri and Anguillara, lately acquired by Virginio Orsini, head of that powerful house. This policy brought Ferdinand I, King of Naples, into conflict with Pope Alexander VI, who was also opposed by Cardinal della Rovere, whose candidature for the papacy had been backed by Ferdinand. Della Rovere fortified himself in his bishopric of Ostia at the Tiber's mouth as Pope Alexander VI formed a league against Naples (25 April 1493) and prepared for war.

Ferdinand allied himself with Florence, Milan, and Venice. He also appealed to Spain for help; but Spain was eager to be on good terms with the papacy to obtain the title to the recently discovered New World. Pope Alexander VI, in the bull Inter Caetera, 4 May 1493, divided the title between Spain and Portugal along a demarcation line. (This and other related bulls are known collectively as the Bulls of Donation.)

In spite of the splendors of the pontifical court, the condition of Rome became every day more deplorable. The city swarmed with adventurers, assassins, prostitutes and informers, murder and robbery were committed with impunity, and the Pope himself cast aside all show of decorum; indulging in the chase, and arranging dancing, and stage plays. One of his close companions was Cem, the brother of the Sultan Bayazid II (1481 – 1512), detained as a hostage. The general outlook in Italy was of the gloomiest and the country was on the eve of foreign invasion.

Pope Alexander VI made many alliances to secure his position. He sought help from Charles VIII of France (1483 – 1498), who was allied to Ludovico "Il Moro" [The Moor, so called because of his swarthy complexion] Sforza, the de facto Duke of Milan who needed French support to legitimize his rule. As King Ferdinand I of Naples was threatening to come to the aid of the rightful duke Gian Galeazzo, the husband of his granddaughter Isabella, Alexander VI encouraged the French king in his plan for the conquest of Naples.

But Pope Alexander VI, always ready to seize opportunities to aggrandize his family, then adopted a double policy. Through the intervention of the Spanish ambassador he made peace with Naples in July 1493 and cemented the peace by a marriage between his son Gioffre and Doña Sancha, another granddaughter of Ferdinand I. In order to dominate the Sacred College of Cardinals more completely, Alexander, in a move that created much scandal, created 12 new cardinals. Among the new cardinals was his own son Cesare, then only 18 years old. Alessandro Farnese (later Pope Paul III), the brother of one of the Pope's mistresses, the beautiful Giulia Farnese, was also among the newly created cardinals.

On 25 January 1494 Ferdinand I died and was succeeded by his son Alfonso II (1494 – 1495). Charles VIII of France now advanced formal claims on the Kingdom of Naples. Pope Alexander VI authorized him to pass through Rome, ostensibly on a crusade against the Turks, without mentioning Naples. But when the French invasion became a reality Pope Alexander VI became alarmed, recognized Alfonso II as king of Naples, and concluded an alliance with him in exchange for various fiefs for his sons (July 1494). A military response to the French threat was set in motion: a Neapolitan army was to advance through the Romagna and attack Milan, while the fleet was to seize Genoa. However, both expeditions were badly conducted and failed, and on 8 September Charles VIII crossed the Alps and joined Lodovico il Moro at Milan. The papal states were in turmoil, and the powerful Colonna faction seized Ostia in the name of France. Charles VIII rapidly advanced southward, and after a short stay in Florence, set out for Rome (November 1494).

Pope Alexander VI appealed to Ascanio Sforza and even to the Turkish sultan for help. He tried to collect troops and put Rome in a state of defense, but his position was precarious. When the Orsini offered to admit the French to their castles, Alexander had no choice but to come to terms with Charles. On 31 December Charles VIII entered Rome with his troops, the cardinals of the French faction, and Giuliano della Rovere. Pope Alexander VI now feared that Charles might depose him for simony, and that the king would summon a council to nominate a new pope. However, Pope Alexander VI was able to win over the bishop of Saint - Malo, who had much influence over the king, with a cardinal's hat. Pope Alexander VI agreed to send Cesare as legate to Naples with the French army, to deliver Cem to Charles VIII, and to give Charles Civitavecchia (16 January 1495). On 28 January Charles VIII departed for Naples with Cem and Cesare, but the latter slipped away to Spoleto. Neapolitan resistance collapsed, and Alfonso II fled and abdicated in favor of his son Ferdinand II. However, Ferdinand was abandoned by all and also had to escape, and the Kingdom of Naples was conquered with surprising ease.

A reaction against Charles VIII soon set in, for all the European powers were alarmed at his success. On 31 March 1495 a so-called Holy League was formed between the Pope, the emperor, Venice, Lodovico il Moro and Ferdinand of Spain. The League was ostensibly formed against the Turks, but in reality it was made to expel the French from Italy. Charles VIII had himself crowned King of Naples on 12 May but a few days later began his retreat northward. He met the allies at Fornovo, and after a drawn battle cut his way through them and was back in France by November. Ferdinand II was reinstated at Naples soon afterwards, with Spanish help. The expedition, if it produced no material results, demonstrated the foolishness of the so-called 'politics of equilibrium', the Medicean doctrine of preventing one of the Italian principates from overwhelming the rest and uniting them under its hegemony. Charles VIII's belligerence in Italy had made it transparent that the 'politics of equilibrium' did nothing but render the country unable to defend itself against a powerful invading force. Italy was shown to be very vulnerable to the predations of the powerful nation - states, France and Spain, that had forged themselves during the previous century. Alexander VI now followed the general tendency of all the princes of the day to crush the great feudatories and establish a centralized despotism. In this manner he was able to take advantage of the defeat of the French in order to break the power of the Orsini. From that time on, Alexander was able to build himself an effective power base in the Papal States.

Virginio Orsini, who had been captured by the Spanish, died a prisoner at Naples, and the Pope confiscated his property. The rest of the Orsini clan still held out however, defeating the papal troops sent against them under Guidobaldo da Montefeltro, Duke of Urbino and Giovanni Borgia, Duke of Gandia, at Soriano (January 1497). Peace was made through Venetian mediation, the Orsini paying 50,000 ducats in exchange for their confiscated lands; the Duke of Urbino, whom they had captured, was left by the Pope to pay his own ransom. The Orsini remained very powerful, and Pope Alexander VI could count on none but his 3,000 Spanish troops. His only success had been the capture of Ostia and the submission of the francophile cardinals Colonna and Savelli.

Then occurred the first of those ugly domestic tragedies for which the house of Borgia remains notorious. On 14 June the Duke of Gandia, lately created Duke of Benevento, disappeared; the next day his corpse was found in the Tiber.

Pope Alexander VI, overwhelmed with grief, shut himself up in Castel Sant'Angelo. He declared that henceforth the reform of the church would be the sole object of his life, a resolution he did not keep. Every effort was made to discover the assassin, and suspicion fell on various highly placed people. When the rumor spread that Cesare, the Pope's second son, had done the deed, the inquiries ceased. No conclusive evidence was ever revealed about the murder, although Cesare remained the most widely suspected.

Violent and vengeful, Cesare now became the most powerful man in Rome, and even his father quailed before him. Because Pope Alexander VI needed funds to carry out his various schemes, he began a series of confiscations, of which one of the victims was his own secretary. The process was a simple one: any cardinal, nobleman or official who was known to be rich would be accused of some offense; imprisonment and perhaps murder followed at once, and then the confiscation of his property. The least opposition to the Borgia was punished with death.

The debased state of the curia was a major scandal. Opponents such as the powerful demagogic Florentine friar Girolamo Savonarola launched invectives against papal corruption and appealed for a general council to confront the papal abuses. Pope Alexander VI, unable to get the excommunicated Savonarola into his own hands, browbeat the Florentine government into condemning the reformer to death (23 May 1498). The houses of Colonna and Orsini, after much fighting between themselves, allied against the Pope, who found himself unable to maintain order in his own dominions.

In these circumstances, Pope Alexander VI, feeling more than ever that he could only rely on his own kin, turned his thoughts to further family aggrandizement. He had annulled Lucrezia's marriage to Giovanni Sforza, who had responded to the suggestion that he was impotent with the counter claim that Pope Alexander VI and Cesare indulged in incestuous relations with Lucrezia, in 1497, and, unable to arrange a union between Cesare and the daughter of King Frederick IV of Naples (who had succeeded Ferdinand II the previous year), he induced Frederick by threats to agree to a marriage between the Duke of Bisceglie, a natural son of Alfonso II, and Lucrezia. Cesare, after resigning his cardinalate, was sent on a mission to France at the end of the year, bearing a bull of divorce for the new French king Louis XII, in exchange for which he obtained the duchy of Valentinois (a duchy chosen because it was consistent with his already known nickname of Valentino), a promise of material assistance in his schemes to subjugate the feudal princelings of papal Romagna, and a marriage to a princess of Navarre.

Pope Alexander VI hoped that Louis XII's help would be more profitable to his house than that of Charles VIII had been. In spite of the remonstrances of Spain and of the Sforza, he allied himself with France in January 1499 and was joined by Venice. By autumn Louis XII was in Italy expelling Lodovico Sforza from Milan. With French success seemingly assured, the Pope determined to deal drastically with the Romagna, which although nominally under papal rule was divided into a number of practically independent lordships on which Venice, Milan, and Florence cast hungry eyes. Cesare, empowered by the support of the French, began to attack the turbulent cities one by one in his capacity as nominated gonfaloniere (standard bearer) of the church. But the expulsion of the French from Milan and the return of Lodovico Sforza interrupted his conquests, and he returned to Rome early in 1500.

While the enterprising explorers of Spain and Portugal were quick to enslave the indigenous peoples met in Africa and the New World, some popes had spoken out against this practice. In 1435, Pope Eugene IV had issued an attack on slavery in his papal bull Sicut Dudum which included the excommunication of all those who engage in the slave trade. However, a form of indentured servitude was allowed, being similar to a peasant's duty to his liege lord in Europe.

In the wake of Columbus landing in the New World, Pope Alexander was asked by the Spanish monarchy to confirm ownership of these found lands. The bulls issued by Pope Alexander VI : "Eximiae devotionis" (3 May 1493), "Inter Caetera" (4 May 1493) and "Dudum Siquidem" (23 September 1493), conferred similar rights to Spain in relation to the new found lands in the Americas as Pope Nicholas V had previously done in the bulls "Romanus Pontifex" and "Dum Diversas". Morales Padron (1979) concludes that these bulls gave power to enslave the natives. Minnich (2005) asserts that this "slave trade" was permitted to facilitate conversions to Christianity. Other historians and Vatican scholars strongly disagree with these accusations and assert that Pope Alexander VI never gave his approval of slavery. Other later popes, such as Pope Benedict XIV in Immensa Pastorium (1741) and Pope Gregory XVI in his letter In Supremo Apostolatus (1839), continued to condemn slavery.

Thornberry (2002) asserts that "Inter Caetera" was applied in the "Requerimiento" which was read to American Indians (who could not understand the colonizers' language) before hostilities against them began. They were given the option to accept the authority of the Pope and Spanish crown or face being attacked and subjugated. In 1993, the Indigenous Law Institute called on Pope John Paul II to revoke "Inter Caetera" and to make reparation for "this unreasonable historical grief". This was followed by a similar appeal in 1994 by the Parliament of World Religions.

The year 1500 was a jubilee year, and crowds of pilgrims flocked to the city from all parts of the world bringing money to donate as a part of the requirements to receive a certain indulgence, so that Pope Alexander VI was able to furnish Cesare with funds for his enterprise. In the north the pendulum swung back again in favor of the French, who reoccupied Milan in April, causing the downfall of the Sforza, much to Pope Alexander VI's satisfaction.

In July, the Duke of Bisceglie, whose existence was no longer advantageous, was murdered on Cesare's orders and practically in the Pope's presence, leaving Lucrezia free to contract another marriage. The Pope, ever in need of money, now created twelve new cardinals, from whom he received 120,000 ducats, and fresh conquests for Cesare were considered. A crusade was talked of, but the real object was central Italy; and so in the autumn, Cesare, backed by France and Venice, set forth with 10,000 men to complete his interrupted business in the Romagna.

The local despots of Romagna were duly dispossessed, and an administration was set up, which, if tyrannical and cruel, was at least orderly and strong. On his return to Rome in June 1501 Cesare was created Duke of Romagna. Louis XII, having succeeded in the north, determined to conquer southern Italy as well. He concluded a treaty with Spain for the division of the Neapolitan kingdom, which was ratified by the Pope on 25 June, Frederick being formally deposed. While the French army proceeded to invade Naples, Pope Alexander VI took the opportunity, with the help of the Orsini, to reduce the Colonna to obedience. In his absence on campaign he left Lucrezia as regent, providing the remarkable spectacle of a pope's natural daughter in charge of the Holy See. Shortly afterwards he induced Alfonso d'Este, son of the Duke of Ferrara, to marry Lucrezia, thus establishing her as wife of the heir to one of the most important duchies in Italy (January 1502). At about this time a Borgia of doubtful parentage was born: Giovanni, described in some papal documents as Pope Alexander VI's son and in others as Cesare's.

As France and Spain were quarreling over the division of Naples and the Campagna barons were quiet, Cesare set out again in search of conquests. In June 1502, he seized Camerino and Urbino, the news of whose capture delighted the Pope; but his attempt to draw Florence into an alliance failed. In July, Louis XII of France again invaded Italy and was at once bombarded with complaints from the Borgias' enemies. The Pope's diplomacy, however, turned the tide, and Cesare, in exchange for promising to assist the French in the south, was given a free hand in central Italy.

A danger now arose in the shape of a conspiracy by the deposed despots, the Orsini, and of some of Cesare's own condottieri. At first the papal troops were defeated and things looked bleak for the house of Borgia. But a promise of French help quickly forced the confederates to come to terms. Cesare, by an act of treachery, then seized the ringleaders at Senigallia and put Oliverotto da Fermo and Vitellozzo Vitelli to death (31 December 1502). When Alexander VI heard the news, he lured Cardinal Orsini to the Vatican and cast him into a dungeon, where he died. His goods were confiscated, his aged mother turned into the street and many other members of the clan in Rome were arrested, while Alexander's son Goffredo Borgia led an expedition into the Campagna and seized their castles. Thus the two great houses of Orsini and Colonna, who had long fought for predominance in Rome and often flouted the Pope's authority, were subjugated and the Borgias' power increased. Cesare then returned to Rome, where his father asked him to assist Goffredo in reducing the last Orsini strongholds; this for some reason he was unwilling to do, much to his father's annoyance; but he eventually marched out, captured Ceri and made peace with Giulio Orsini, who surrendered Bracciano.

Three more high personages fell victim to the Borgias' greed this year: Cardinal Michiel, who was poisoned in April 1503, J. da Santa Croce, who had helped to seize Cardinal Orsini, and Troches or Troccio, Alexander's chamberlain and secretary; all these murders brought immense sums to the Pope. About Cardinal Ferrari's death, there is more doubt; he probably died of fever, but Alexander VI immediately confiscated his goods anyway. The war between France and Spain for the possession of Naples dragged on, and the Pope was forever intriguing, ready to ally himself with whichever power promised the most advantageous terms at any moment. He offered to help Louis XII on condition that Sicily be given to Cesare, and then offered to help Spain in exchange for Siena, Pisa and Bologna.

Although there is no doubt that Alexander VI liked to eliminate any cardinal and immediately confiscate his property, there is no sufficient evidence on the methods used in these murders. It has been suggested that the family used their favorite poison Cantarella, an arsenic variation, which was offered to their poor victim in a form of drink with an innovative nickname, the "liquor of succession." Since raw forms of arsenic then known were not immediately fatal, Alexander VI must have had a method invented for the preparation of this substance, but no confirmation of this has survived. The famous cup of Borgia, a golden cup with a hidden area storing the poison so it could be mixed with the wine, is often mentioned as the family's favorite murdering method, and it has been the base for many legendary and crime stories, including Agatha Christie's short story The Apples of Hesperides published in the 1947 collection The Labours of Hercules.

Burchard recorded the events that surrounded the death of the Pope. Cesare was preparing for another expedition in August 1503 when, after he and his father had dined with Cardinal Adriano da Corneto on 6 August, they were taken ill with fever. Cesare eventually recovered, but the Pope was too old to have any chance. According to Burchard, his stomach became swollen and turned to liquid, while his face became wine colored and his skin began to peel off. Finally his stomach and bowels bled profusely. After more than a week of intestinal bleeding and convulsive fevers, and after accepting last rites and making a confession, the despairing Alexander VI died on 18 August 1503 at the age of 72. He is believed to have uttered the last words, "I'll come, I'll come. It's normal for you to call me. But wait a bit more", before his death.

His death was followed by scenes of wild disorder, and Cesare, too ill to attend to the business himself, sent Don Michelotto, his chief bravo, to seize the Pope's treasures before the death was publicly announced. When the body was exhibited to the people the next day it was in a shocking state of decomposition. Writing in his Liber Notarum, Burchard elaborates: "The face was very dark, the color of a dirty rag or a mulberry, and was covered all over with bruise - colored marks. The nose was swollen; the tongue had bent over in the mouth, completely double, and was pushing out the lips which were, themselves, swollen. The mouth was open and so ghastly that people who saw it said they had never seen anything like it before." It has been suggested that, having taken into account the unusual level of decomposition, Alexander VI was accidentally poisoned to death by his son, Cesare, with Cantarella (which had been prepared to eliminate Cardinal Adriano), although some commentaries doubt these stories and attribute the Pope's death to malaria, then prevalent in Rome, or to another such pestilence. The ambassador of Ferrara wrote to Duke Ercole that it was no wonder the Pope and the duke were sick because nearly everyone in Rome was ill because of bad air ("per la mala condictione de aere").

Burchard described how the Pope's mouth foamed like a kettle over a fire and how the body began to swell so much that it became as wide as it was long. The Venetian ambassador reported that Rodrigo Borgia's body was "the ugliest, most monstrous and horrible dead body that was ever seen, without any form or likeness of humanity." Finally the body began to release sulfurous gases from every orifice. Burchard records that he had to jump on the body to jam it into the undersized coffin and covered it with an old carpet, the only surviving furnishing in the room.

Such was Alexander VI's unpopularity that the priests of St. Peter's Basilica refused to accept the body for burial until forced to do so by papal staff. Only four prelates attended the Requiem Mass. Alexander VI's successor on the Throne of St. Peter, Francesco Todeschini - Piccolomini, who assumed the name of Pius III (1503), forbade the saying of a Mass for the repose of his predecessor's soul, saying, "It is blasphemous to pray for the damned." After a short stay, the body was removed from the crypts of St. Peter's and installed in a less known church, the Spanish national church of Santa Maria in Monserrato degli Spagnoli.

Alexander VI was known for his patronage of the arts, and in his days a new architectural era was initiated in Rome with the coming of Bramante. Raphael, Michelangelo and Pinturicchio all worked for him. He commissioned Pinturicchio to lavishly paint a suite of rooms in the Apostolic Palace in the Vatican, which are today known as the Borgia Apartment.

In addition to the arts, Alexander VI also encouraged the development of education. In 1495, he issued a papal bull at the request of William Elphinstone, Bishop of Aberdeen, and King James IV of Scotland, founding King's College, Aberdeen. King's College now forms an integral element of the University of Aberdeen.

Alexander VI, allegedly a marrano according to papal rival Giuliano della Rovere, distinguished himself by his relatively benign treatment of Jews. After the 1492 expulsion of Jews from Spain, some 9,000 impoverished Iberian Jews arrived at the borders of the Papal States. Alexander welcomed them into Rome, declaring that they were "permitted to lead their life, free from interference from Christians, to continue in their own rites, to gain wealth, and to enjoy many other privileges." He similarly allowed the immigration of Jews expelled from Portugal in 1497 and from Provence in 1498.

It has been noted that the crimes of Alexander VI are similar in nature to those of other Renaissance princes, with the one exception being his position in the Church. As De Maistre said in his work Du Pape, "The latter are forgiven nothing, because everything is expected from them, wherefore the vices lightly passed over in a Louis XIV become most offensive and scandalous in an Alexander VI."

Bohuslav Hasištejnský z Lobkovic, a Bohemian humanist poet (1461 – 1510) dedicated one of his Latin poems to Alexander: