Alba's grandfather, Fadrique Álvarez de Toledo, educated him in military science and politics; and he was engaged with distinction at the Battle of Pavia in 1525, while still a youth.

Selected for a military command by Charles V, he took part in the siege of Tunis (1535), and successfully defended Perpignan against the dauphin of France. He was present at the Battle of Mühlberg (1547), and the victory gained there over the Prince - Elector Johann Friederich of Saxony was due mainly to his exertions. He took part in the subsequent successful siege of Wittenberg defended by the Electress, Sybille, following which Alba presided at the court martial which tried the Prince - Elector and condemned him to death as a rebel against the Emperor, wringing from him the Capitulation of Wittenberg (1547), in which he was compelled to resign the electoral dignity and a great part of his territory to his cousin Maurice.

In 1552 Alba was entrusted with the command of the army intended to invade France, and was engaged for several months in an unsuccessful siege of Metz. In consequence of the success of the French arms in Piedmont, he was made commander - in - chief of all the emperor's forces in Italy, and at the same time invested with unlimited power. Success did not, however, attend his first attempts, and after several unfortunate attacks he was obliged to retire into winter quarters.

After the abdication of Charles V he was continued in the command by Philip II, who, however, restrained him from extreme measures. Alba had subdued the whole Campagna and was at the gates of Rome, when he was compelled by Philip's orders to negotiate a peace.

Not long after this (1559) he was sent at the head of a splendid embassy to Paris to espouse, in the name of Philip, Elizabeth, daughter of Henry, king of France. These negotiations led to the Peace of Cateau - Cambrésis.

In 1567, Philip, who was a zealous opponent of Protestantism, sent Alba into the Netherlands at the head of an army of 12,000 men, with unlimited powers for the extirpation of the heretics. Alba quickly erected a tribunal, the Council of Troubles, which soon became known to the Calvinists as the "Council of Blood," to try all persons who had been engaged in the late commotions that the rule of Philip had excited. During the ten years it operated, thousands of people were executed. The precise number is disputed: Dutch sources cite 18,000 victims, while Spanish accounts mention only a few hundred. About 12,000 casualties can be considered as the most accurate estimate, of which 1,083 were executed. Alba imprisoned the Count of Egmont and the Count of Hoorn, the two popular leaders of the dissatisfied Dutch nobles, and had them condemned to death even though they were Catholics.

Alba attempted to raise money by imposing the Spanish alcabala, a tax of 10% on all sales ("tenth penny" tax) on the Low Countries, and this aroused the opposition of many Catholic residents as well. The exiles from the Low Countries, who called themselves Geuzen (French gueux, "beggars"), encouraged by the general resistance to his government, fitted out a fleet of privateers, and after strengthening themselves by successful depredations, seized the town of Den Briel (Brielle). Thus Alba, by his unrelenting harshness, became the unwitting instrument of the future independence of the seven Dutch provinces.

On August 22, Alba, accompanied by a body of select Spanish troops, made his entry into Brussels. He immediately appointed a council to condemn without trial those suspected of heresy and rebellion. On June 1, 1568, Brussels witnessed the simultaneous decapitation of twenty-two noblemen; on 6 June followed the execution of the Counts of Egmond and Hoorne.

The fleet of the exiles, having met the Spanish fleet, defeated it and reduced Holland and Mons. The States of Holland, assembling at Dordrecht in 1572, openly declared against Alba's government, and marshaled under the banners of the prince of Orange.

Alba's preparations to defeat the gathering storm were made with his usual rapidity and vigour, and he succeeded in recovering Mons, Mechelen and Zutphen, under the conduct of his son Don Fadrique. All three cities were sacked and many civilians killed. With the exception of Zeeland and Holland, he regained all the provinces; and at last his son stormed Naarden, massacring every man, woman and child, proceeded to invest the city of Haarlem, which, after standing an obstinate siege, was taken and pillaged. Their next attack was upon Alkmaar; but there they were met with such desperate resistance that Alba was forced to retire.

Alba's feeble health and continued lack of success induced him to solicit his recall from the government of the Low Countries. In December 1573 Philip accepted his resignation and replaced him with Luis de Zúñiga y Requesens.

On his return he was treated for some time with great distinction by Philip, until a love affair of Don Fadrique dragged father and son into disgrace. Alba was banished from court and retired to the castle of Uceda.

Alba remained in exile at his castle up to 1580, when his leadership was sought again in the war against Portugal.
Alba remained in exile two years, when the success of António, Prior of Crato, in assuming the crown of Portugal caused Philip to turn to Alba as the man whose ability and fidelity he could most rely on. Made supreme commander in Portugal in 1580, Alba soon defeated António in the Battle of Alcântara, drove him from the kingdom, and reduced Portugal to the subjection of Philip. Entering Lisbon he seized an immense treasure, and allowed his soldiers to sack the suburbs and vicinity. Alba, however, did not enjoy the honors and rewards of his last expedition, for he died at Lisbon on December 11, 1582.

In 1527, the Duke married his cousin María Enríquez de Toledo y Guzmán, daughter of Diego Enríquez de Guzmán, 3rd Count of Alba de Liste, with whom he had four children.