Petrarch says he was born on Garden Street in the city of Arezzo, just at dawn on a Monday. He was the son of Ser Petracco. He spent his early childhood in the village of Incisa, near Florence. Petrarch spent much of his early life at Avignon and nearby Carpentras, where his family moved to follow Pope Clement V who moved there in 1309 to begin the Avignon Papacy. He studied law at Montpellier (1316–20) and Bologna (1320–23) with a lifelong friend and schoolmate called Guido Sette. Because his father was in the profession of law he insisted that Petrarch and his brother study law also. Petrarch however was primarily interested in writing and Latin literature and considered these seven years wasted. Additionally he proclaimed that through legal manipulation his guardians robbed him of his small property inheritance in Florence, which only reinforced his dislike for the legal system. He protested, "I couldn't face making a merchandise of my mind", as he viewed the legal system as the art of selling justice.

Petrarch was a prolific letter writer and counted Boccaccio among his notable friends to whom he wrote often. After the death of their parents, Petrarch and his brother Gherardo went back to Avignon in 1326, where he worked in numerous clerical offices. This work gave him much time to devote to his writing. With his first large scale work, Africa, an epic in Latin about the great Roman general Scipio Africanus, Petrarch emerged as a European celebrity. On April 8, 1341, he became the first poet laureate since antiquity and was crowned on the holy grounds of Rome's Capitol.

He traveled widely in Europe and served as an ambassador and has been called "the first tourist" because he traveled just for pleasure, which was the basic reason he climbed Mont Ventoux. During his travels, he collected crumbling Latin manuscripts and was a prime mover in the recovery of knowledge from writers of Rome and Greece. He encouraged and advised Leontius Pilatus's translation of Homer from a manuscript purchased by Boccaccio, although he was severely critical of the result. Petrarch had acquired a copy, which he did not entrust to Leontius, but he knew no Greek; Homer, Petrarch said, "was dumb to him, while he was deaf to Homer". In 1345 he personally discovered a collection of Cicero's letters not previously known to have existed, the collection ad Atticum. Disdaining what he believed to be the ignorance of the centuries preceding the era in which he lived, Petrarch is credited with creating the concept of a historical "Dark Ages".

Petrarch claimed that on April 26, 1336, with his brother and two servants, he climbed to the top of Mont Ventoux (either 1,912 meters (6,273 ft) or 6,263 feet (1,909 m)). Petrarch made the climb of his own volition, i.e. for pleasure, rather than any necessary journey. He wrote an account of the trip, composed considerably later, as a letter to his friend Dionigi di Borgo San Sepolcro. The accuracy of Petrarch's account is open to question; particularly the assertions that he was the first to climb a mountain for pleasure since Philip V of Macedon, and that an aged peasant had warned him off the unclimbable mountain. Jean Buridan had climbed the same mountain a few years before, and other ascents are recorded from the Middle Ages, including Anno II, Archbishop of Cologne.

J.H. Plumb writes in his book The Italian Renaissance of Morris Bishop's version of Petrarch's ascent of Mont Ventoux showing Petrarch's letter on the ascent to his confessor, the monk Dionigi di Borgo San Sepolcro, rings of aesthetic gratification from grandeur and majesty, a modern attitude that is quoted to this day in many books and journals pertaining to mountaineering. In the Confessions, Petrarch's eyes were immediately drawn to the following words:

"And men go about to wonder at the heights of the mountains, and the mighty waves of the sea, and the wide sweep of rivers, and the circuit of the ocean, and the revolution of the stars, but themselves they consider not.",

Petrarch's response was to turn from the outer world of nature to the inner world of 'soul':

I closed the book, angry with myself that I should still be admiring earthly things who might long ago have learned from even the pagan philosophers that nothing is wonderful but the soul, which, when great itself, finds nothing great outside itself. Then, in truth, I was satisfied that I had seen enough of the mountain; I turned my inward eye upon myself, and from that time not a syllable fell from my lips until we reached the bottom again. [...] [W]e look about us for what is to be found only within. [...] How many times, think you, did I turn back that day, to glance at the summit of the mountain which seemed scarcely a cubit high compared with the range of human contemplation [...]

James Hillman argues that this rediscovery of the inner world is the real significance of the Ventoux event. The Renaissance begins not with the ascent of Mont Ventoux but with the subsequent descent — the "return [...] to the valley of soul", as Hillman puts it.

The later part of Petrarch's life he spent in journeying through northern Italy as an international scholar and poet-diplomat. His career in the Church did not allow him to marry, but he did father two children by a woman or women unknown to posterity. A son, Giovanni, was born in 1337, and a daughter, Francesca, was born in 1343. Both he later legitimized. Giovanni died of the plague in 1361. Francesca married Francescuolo da Brossano (who was later named executor of Petrarch's will) that same year. In 1362, shortly after the birth of a daughter, Eletta (same name as Petrarch's mother), they joined Petrarch in Venice to flee the plague then ravaging parts of Europe. A second grandchild, Francesco, was born in 1366, but died before his second birthday. Francesca and her family lived with Petrarch in Venice for five years from 1362 to 1367 at Palazzo Molina; although Petrarch continued to travel in those years. About 1368 Petrarch and his daughter Francesca (with her family) moved to the small town of Arquà in the Euganean Hills near Padua, where he passed his remaining years in religious contemplation. He died in his house in Arquà on July 19, 1374 – one day short of his seventieth birthday.

Petrarch's will (dated April 4, 1370) leaves 50 florins to Boccaccio "to buy a warm winter dressing gown"; various legacies (a horse, a silver cup, a lute, a Madonna) to his brother and his friends; his house in Vaucluse to its caretaker; for his soul, and for the poor; and the bulk of his estate to his son-in-law, Francescuolo da Brossano, who is to give half of it to "the person to whom, as he knows, I wish it to go"; presumably his daughter, Francesca, Brossano's wife. The will mentions neither the property in Arquà nor his library; Petrarch's library of notable manuscripts was already promised to Venice, in exchange for the Palazzo Molina. This arrangement was probably cancelled when he moved to Padua, the enemy of Venice, in 1368. The library was seized by the lords of Padua, and his books and manuscripts are now widely scattered over Europe. Nevertheless, the Biblioteca Marciana traditionally claimed this bequest as its founding, although it was in fact founded by Cardinal Bessarion in 1468.