Begun in 1558 for Angelo Giovanni Spinola, Ambassador to Spain and Emperor Charles the Fifth's banker, the building was completed in 1576 under his son Giulio's direction. It was thanks to him that the hill behind the building was leveled, around 1580, thus allowing the courtyard and garden to be amplified. The project's designer was the architect Giovanni Ponzello. Since the beginning of the 1900s it has housed bank office spaces.
The frescoes by the Calvi brothers, to which perhaps Lazzaro Tavarone also contributed, are scarcely visible on the building's facade. Both the building's facade and its frescoes in the atrium are intended to honor the building's patrons.