He was originally destined to follow the profession of his father, a gold- and silver-smith, but he manifested so much skill and taste in designing that he was placed under the supervision of two Florentine artists, Ignazio Hugford and Giovanni Domenico Ferretti, who instructed him in painting.

He then moved for a short time in 1762 to Rome, where he completed a set of engravings representing frescoes at Grottaferrata by Domenichino depicting the life of St Nilus.

He produced an enormous number of engravings, including Clytie after Annibale Carracci, and of the Virgin and Child, after Carlo Dolci.

As his prominence grew, he took on students including Michele Benedetti, Ignatius Joseph van den Berghe, Thomas Cheesman, Lambertus Antonius Claessens, Daniel Gardner, Christiaan Josi, Johan Fredrik Martin, Conrad Martin Metz, Luigi Schiavonetti, John Keyse Sherwin, Heinrich Sintzenich, Peltro William Tomkins, Domenico Bernardo Zilotti,[4] and Gavriil Skorodumov.

[5][6] His son Gaetano Stefano Bartolozzi, born in 1757, also became an engraver and later fathered Madame Vestris a celebrated English actress, opera singer, and theater manager.

In 1802, Bartolozzi accepted the post of director of the National Academy of Lisbon and moved there with the intention of reforming the royal press and producing an edition of the Portuguese epic poem The Lusiads (Os Lusíadas).