At the beginning of his career Perino del Vaga worked in Raphael’s workshop, where he assisted with the frescos in the Vatican Loggias. After Raphael’s death he remained connected with the workshop, which was now run by Giulio Romano, and established himself as a specialist for fresco painting. He undertook commissions in the Vatican, in private palaces and several churches. The plundering of Rome by soldiers of the imperial army in 1527 resulted in the collapse of the art market in Rome and, for a period, Perino del Vaga moved into the service of Andrea Doria in Genoa.

After returning to Rome in 1538 he established a large studio and completed commissions in the private apartments of Pope Paul III, in the Sala Regia of the Vatican and in the Castel Sant' Angelo. According to his biographer, Giorgio Vasari, this successful and dedicated artist died from overwork. His oeuvre documented the transition from the High Renaissance to Mannerism.