Cambiaso was precocious, and at the age of fifteen he painted, along with his father, some subjects from Ovid's Metamorphoses on the facade of a house in Genoa.
In 1544, at the age of seventeen, he was involved in the decoration of the Palazzo Doria, now the Prefettura, perhaps working with Marcantonio Calvi, a painter of his father's generation.
He aided in the vault decoration of the church of San Matteo, in collaboration with Giovanni Battista Castello.
In the Capella Lercari of the Duomo di San Lorenzo, Cambiaso frescoed a Presentation and Marriage of the Virgin in 1569, remainder of chapel by Castello.
In 1583 Cambiaso accepted an invitation from Philip II to complete for the Escorial a series of frescoes begun by Castello; and the 1911 Encyclopædia states the principal reason for traveling to Spain was that he hoped royal influence would gain favor with the Vatican for his marriage plans, but this failed.
His fresco technique was very spontaneous and he used small drawings to create full-size sketches on the walls without the aid of cartoons.
In the mid-1560s he began to draw in a simplified, geometric style that may have been inspired by similar works by Albrecht Dürer and other German artists.