The third palace on the sea side of Via dei Balbi, but the last in the building history of the seventeenth-century street, it was erected between 1656 and 1674 at the behest of Francesco Maria Balbi, who entrusted the architect Pietro Antonio Corradi with its design.

In the early 18th century, the new owners initiated a major architectural renovation and decoration project, together with the acquisition of a magnificent collection of paintings that found their place in the rooms and small gallery of the mansion's main flat.

The collection was largely alienated with the transfer of the building to Marcello Luigi Durazzo in 1824, but some prestigious works, among those that were not sold, were transferred to the Spinola palace in Piazza Pellicceria, which has now become the Galleria Nazionale di Palazzo Spinola, where the public can still admire them.

In 1890, the palace was bought by the Genoese entrepreneur Edilio Raggio, who started a further transformation, demolishing the interiors and obtaining flats. At the same time, the façade was redesigned in the Genoese neo-Baroque style, the vast atrium overlooking a small courtyard behind was created, and the great monumental staircase, supported by rampant arches and cross vaults, was built.

The vault of the staircase was decorated with a cycle of wall tempera paintings dedicated to Risorgimento allegories and the celebration of the Savoy monarchy and the unified state. In one of the reception rooms, Nicolò Barabino's pupil, Luigi Gainotti, frescoed the Allegory of Liguria.

Starting in the 1950s, the palace became the seat of the University of Genoa.