The edifice was constructed in 1593 as per the will of Francesco Grimaldi on the pre-existent Medieval foundations. Pier Paolo Rubens left us precious documentation of the first version of the mansion when he included an etching of the façade in the volume ‘The Mansions of Genoa’ which he published in Antwerp in 1622. Thanks to this the original connection between the two wings of the mansion with an open loggia is documented, closed in the mid seventeenth century, in correspondence with the third storey, with a terrace whereupon the gallery of mirrors was constructed in 1734. The original frescoed décor can with the blind architectural details may also be seen; several sections of which have been recovered recently and from which the continuity of the elaboration between the external facades and the frescoed décor is visible in the halls of the second storey.
The museum was conceived with the artwork, furnishings, ceramics, silver, books and etchings which the marquis Paolo and Franco Spinola donated in 1958 to the Italian State together with the centuried family mansion of which the aforementioned constituted patrimony. Condition of the donation was the maintenance of the aspect of a residence which characterizes the mansion with exception of the last two stories. Here, aware that the damage of the war had cancelled the historical aspect and therefore that this condition did not have apply, they suggested the arrangement of a different museum, and therefore created the National Gallery of Liguria. As per their intentions, this part of the mansion was opened in 1993 to present to the public the nucleus of the works which today enrich the patrimony of the museum established by the acquisitions of the State turned at increasing, in a complementary manner, the donation of Spinola.