He was originally destined to follow the profession of his father, who was a gold- and silver-smith; but he manifested so much skill and taste in designing that he was placed under the superintendence of two Florentine artists, who instructed him in painting. After devoting three years to that art, he went to Venice and studied engraving. He made very rapid progress, and executed some works of considerable importance at Venice. He then removed for a short time to Rome, where he completed a set of engravings representing events from the life of St Nilus, and, after returning to Venice, set out for London in 1764.
For nearly forty years he resided in London, and produced an enormous number of engravings, the best being those of Clytie, after Annibale Caracci, and of the Virgin and Child, after Carlo Dolci. A great proportion of them are from the works of Cipriani and Angelica Kauffmann. Bartolozzi also contributed a number of plates to Boydell's Shakespeare Gallery.
In 1802 he was invited to Lisbon as director of the National Academy. He remained in Portugal till his death. His son Gaetano Stephano (1757-1821), also an engraver, was the father of Madame Vestris.