He was born in Florence, and initially worked under Albertinelli until about 1506. In 1505 he befriended Andrea del Sarto; and by the next year, the two painters set up common shop in the Piazza del Grano. He was proficient in fresco and Vasari claimed that he surpassed all his contemporaries in this method. It however in his portraits, and not religious paintings and frescoes, that his painting gathers naturalistic power.
In 1513, in the cloister of the Annunziata he frescoed the Marriage of the Virgin, part of a larger series mainly directed by Andrea del Sarto, and overshadowed by the latter's masterpiece of Birth of the Virgin. Other artists working under Sarto at the cloister included Rosso Fiorentino, Pontormo, Francesco Indaco, and Baccio Bandinelli.
In 1514, he frescoed a Mategnesque Last Supper for the Convento della Calza in Florence. In 1518-19, at the Convento della Salzo, in another series of frescoes on which Andrea was likewise employed, he executed the Departure of John the Baptist for the Desert, and the Meeting of the Baptist with Jesus.
In 1520-21, at the villa Medici at Poggio a Caiano he frescoed a turgid Triumph of Cicero on the walls of the salon, but again he is overshadowed by Potormo's naturalistic lunette of Vertumnus and Pomona. The array of figures appears distraught rather than celebratory, the antique details are a melange of quotations, and the architect a fancy of Quattrocento style. He painted a St Job altarpiece (1516, Uffizi).
Various works which have been ascribed to Raphael are reasonably deemed to be by Franciabigio. Such as the Madonna del Pozzo, with its awkwardly muscular John the Baptist; and some of his portraits, including the half figure of a Young Man (shown above). These two works show a close analogy in style to another in the Pitti gallery, avowedly by Franciabigio, a Youth at a Window, and to some others—which bear this painter's recognized monogram.
The series of portraits, taken collectively, placed beyond dispute the eminent and idiosyncratic genius of the master. Two other works of his, of some celebrity, are the Calumny of Apelles, in the Pitti Palace, and the Bath of Bathsheba (painted in 1523), in the Dresden gallery.