The exact details of his birth are uncertain. A number of sources state that he was born in Paris and that his mother was a Parisian, but others denounce this as a romanticism by the earliest biographers. In this case his birthplace was possibly in Tuscany, perhaps in Certaldo, the town of his father. He was the son of a Florentine merchant and an unknown woman, and almost certainly born illegitimate.

Boccaccio grew up in Florence. His father was working for the Compagnia dei Bardi and in the 1320s married Margherita dei Mardoli, of an illustrious family. It is believed Boccaccio was tutored by Giovanni Mazzuoli and received from him an early introduction to the works of Dante. In 1326 Boccaccio moved to Naples with the family when his father was appointed to head the Neapolitan branch of his bank. Boccaccio was apprenticed to the bank, but it was a trade for which he had no affinity. He eventually persuaded his father to let him study law at the Studium in the city. For the next six years Boccaccio studied canon law there. From there he pursued his interest in scientific and literary studies.

His father introduced him to the Neapolitan nobility and the French-influenced court of Robert the Wise in the 1330s. At this time he fell in love with a married daughter of King Robert of Naples (known as Robert the Wise) and she is immortalized as the character "Fiammetta" in many of Boccaccio's prose romances, particularly Il Filocolo (1338). Boccaccio became a friend of fellow Florentine Niccolò Acciaioli, and benefited from his influence as the administrator, and perhaps the lover, of Catherine of Valois-Courtenay, widow of Philip I of Taranto. Acciaioli later became counsellor to Queen Joan I of Naples and, eventually, her Grand Seneschal.

It seems Boccaccio enjoyed law no more than banking, but his studies allowed him the opportunity to study widely and make good contacts with fellow scholars. His early influences included Paolo da Perugia (a curator and author of a collection of myths, the Collectiones), the humanists Barbato da Sulmona and Giovanni Barrili, and the theologian Dionigi di Borgo San Sepolcro.

In Naples, Boccaccio began what he considered his true vocation, poetry. Works produced in this period include Filostrato and Teseida (the source for Chaucer's Troilus and Criseyde and The Knight's Tale respectively), Filocolo, a prose version of an existing French romance, and La caccia di Diana, a poem in terza rima listing Neapolitan women. The period featured considerable formal innovation, including possibly the introduction of the Sicilian octave to Florence, where it influenced Petrarch.

Boccaccio returned to Florence in early 1341, avoiding the plague in that city of 1340, but also missing the visit of Petrarch to Naples in 1341. He had left Naples due to tensions between the Angevin king and Florence. His father had returned to Florence in 1338, where he had gone bankrupt. His mother died shortly afterward. Although dissatisfied with his return to Florence, Boccaccio continued to work, producing Comedia delle ninfe fiorentine (also known as Ameto) a mix of prose and poems, in 1341, completing the fifty canto allegorical poem Amorosa visione in 1342, and Fiammetta in 1343. The pastoral piece Ninfale fiesolano probably dates from this time also. In 1343 Boccaccio's father re-married, to Bice del Bostichi. His children by his first marriage had all died (except Boccaccio) but he had another son, Iacopo, in 1344.

In Florence, the overthrow of Walter of Brienne brought about the government of popolo minuto. It diminished the influence of the nobility and the wealthier merchant classes and assisted in the relative decline of Florence. The city was hurt further, in 1348, by the Black Death, later represented in the Decameron, which killed some three-quarters of the city's population.

From 1347 Boccaccio spent much time in Ravenna, seeking new patronage, and despite his claims, it is not certain whether he was present in plague-ravaged Florence. His stepmother died during the epidemic and his father, as Minister of Supply in the city was closely associated with the government efforts. His father died in 1349 and as head of the family Boccaccio was forced into a more active role.

Boccaccio began work on the Decameron around 1349. It is probable that the structures of many of the tales date from earlier in his career, but the choice of a hundred tales and the frame-story lieta brigata of three men and seven women dates from this time. The work was largely complete by 1352. It was Boccaccio's final effort in literature and one of his last works in Italian, the only other substantial work was Corbaccio (dated to either 1355 or 1365). Boccaccio revised and rewrote the Decameron in 1370-1371. This manuscript has survived to the present day.

From 1350 Boccaccio, although less of a scholar, became closely involved with Italian humanism and also with the Florentine government. His first official mission was to Romagna in late 1350. He revisited that city-state twice and also was sent to Brandenburg, Milan, and Avignon. He also pushed for the study of Greek, housing Barlaam of Calabria, and encouraging his tentative translations of works by Homer, Euripides, and Aristotle.