Fontana was born in Bologna, and became a pupil of Innocenzo da Imola. He afterwards worked for Perin del Vaga in the Palazzo Doria in Genoa. Towards 1550, it is reported that Michelangelointroduced him to Pope Julius III as a portrait-painter; and he was pensioned at the pontifical court. He later joined Vasari's studio in Florence, and worked in frescoes at the Palazzo Vecchio (1563–65). He is an early representative of the Bolognese school of painting. Sabbatini, Samacchini and Passerotti were three of his principal pupils or colleagues. His daughter, Lavinia Fontana, was also a prominent painter.
Returning to Bologna, after doing some work in Fontainebleau (France) and in Genoa, he opened a school of art, in which he became briefly the preceptor of Lodovico and Agostino Carracci. He has left a large quantity of work in Bologna. His altarpiece of the Adoration of the Magi, in the church of Santa Maria delle Grazie, being considered his masterpiece. It is not unlike the style of Paolo Veronese. He died in Rome in 1597.