Built starting in 1562 at the behest of Baldassarre Lomellini by architect Giovanni Ponzello, the building belonged for a long time to the Salvago family, who acquired the property at the end of the 16th century and then sold it to Cristoforo Spinola, ambassador of the Republic of Genoa in Paris. The latter renovated its architectural forms and decorations in a neoclassical style. It was later acquired by Domenico Serra and the Campanella family and later heavily damaged by bombing during World War II.

Evidence of the first phase of the building, frescoed by Andrea Semino and Giovanni Battista Castello with episodes from Roman history and Stories of Aeneas, remains today thanks to the reliefs that Pietro Paolo Rubens included in the collection Modern Palaces of Genoa, published in Antwerp in 1652.

The eighteenth-century interventions commissioned by Cristoforo Spinola modified both the layout and the decorative aspect of the sixteenth-century palace. Organised by the French architect Charles de Wailly and Emanuele Andrea Tagliafichi, the restoration work gave the residence a new neoclassical layout and an oval atrium on the ground floor.

The salon on the piano nobile, henceforth known as the 'Salone del Sole', and the two neoclassical temples on the terrace were then completely renovated.