Duke Luigi Braschi Onesti, a nephew of Pope Pius VI, bought the site in 1790 with papal funds. A 16th-century palace by Sangallo the Younger for the Orsini family was demolished to make way. Cosimo Morelli designed the new palace in the Neoclassical style. Giuseppe Valadier designed the chapel on the piano nobile.
Construction was suspended in February 1798 during the French occupation. Luigi moved in during 1809, and he died in 1816 with the palace still unfinished. Eighteen red granite columns line the monumental staircase, reportedly salvaged from a gallery built by Caligula along the Tiber.
The Italian State bought it in 1871 and used it for the Ministry of the Interior. The Museo di Roma has occupied it since a restoration in 1952.

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