The initial design was made reputedly by Cosimo Fanzago in the late 16th century.
In 1754–1762, the architects Mario Gioffredo and later Luigi Vanvitelli refurbished the palace as we mainly see it today, for the Duchess Marianna de Sangro di Casacalenda.
It is said that during this construction, the Byzantine-era church of Santa Maria della Rotonda was demolished.
The design of monumental pilasters of the top floors of the facade are attributed to Mario Gioffredo.
In 1831, the palace was sold by the Sangro family to the Del Balzo family In 1922, as part of the urban renewal of Naples and to widen Via Mezzocannone, the easternmost bay of the palace was demolished, requiring the removal of frescoes from this part of the piano nobile.