The son of Filippo and pupil of Botticelli, he was enrolled in the Company of San Luca in 1472, as was Leonardo, and was a close friend of his, as shown by their exchanges of commissions for paintings.
In 1478 Leonardo was commissioned to paint the altarpiece for the Chapel of San Bernardo in Palazzo della Signoria, which had originally been commissioned of Piero del Pollaiolo. Leonardo failed to complete the work, although he had done a cartoon that, after being temporarily assigned to Ghirlandaio, was used by Filippino to finish the work in 1485.
In 1501 Lippi left to him the task of painting an altarpiece of Saint Anne for the high altar of Santissima Annunziata, a work that Leonardo undertook but failed to finish.
Ugolino Verino (1438-1516) jokingly hailed Filippino and Leonardo as the «new Apelles and the new Protogenes» (the latter recalled chiefly for his proverbial slowness in completing a painting).
Among his major works in Florence are: the Apparition of the Virgin to St. Bernard (in the Badia Fiorentina), the frescoes in the Brancacci Chapel at the church of the Carmine (along with those of Masaccio), the Virgin and Saints and the Adoration in the Uffizi, and the frescoes in the Strozzi Chapel in Santa Maria Novella. His Annunciation is now in the Museum of Gimignano.