Born in San Gimignano, Tuscany, Buonaccorsi moved to Rome in 1462 and became a student of the homosexual humanist Pomponio Leto, in whose hous he also lived. Buonaccorsi life took a dramatic turn in 1468, when he was accused of having conspired against pope Paul II. he managed to avoid arrest by flight, but the homosexual erses which were found in his papers then earned him a reputation for sodomy.

Among the youths hailed in his poems was Antonio Lepido, another of Leto's students, whom "Callimachus Experientis" (Buonaccorsi's humanist name) called his "Ganymede". The poem also referred to Lucio Fazini, who became bishop of Segni in 1841, as "Lucidus Phosphorus" (Beares of Light).

After various peregrinations Buonaccorsi took refuge in the court of the king of Poland, who named him tutor to the royal princes. In 1474 he became royal secretary, in 1476-77 he served as ambassador to Constantinople, and in 1486 became the king's representative in Venice.

Buonaccorsi was the author of poetical, philosophical and historical works which, after the scandal which led to his exile, prudently became exclusively "heterosexual". With the accession to the Polish trone of his former pupil Jan Olbracht, Buonaccorsi influence peaked. He died and was interred in Cracow, where his tomb can still be seen.