The construction of the palace was began in 1451 by Pope Paul II Barbo when he was the titular Cardinal of the nearby Basilica di S. Marco and continued in 1464 whe he was elected Pope. The work was later carried on by his nephew Marco Barbo. 

The design of the building, typical of 15th century palaces of Roman nobles, reveals Tuscan influence, especially in the “loggia delle benedizioni” and in the incomplete loggia overlooking the courtyard. When it became the property of Lorenzo Cibo, nephew of Pope Innocent VIII, the building was enlarged along via del Plebiscito. In the 18th century, Cardinal Querini has the sentry walkway overlooking via degli Astalli covered in, creating the so-called “corridor of the cardinals”. 

In 1911, to provide space for the monument to Victor Emanuel II on the far side of Piazza Venezia, the entire “greenhouse” of Paul II, which cornered on the main prospect, was moved and reconstructed with all its stones, marble and cloisters on the left side of the building.

The Palazzo Venezia was designated as the seat of the museum in 1916 when it passed into the possession of the Italian State after serving as the embassy of the Venetian Republic and late ras the Austrian embassy. From 1929 to 1943 it was chosen by Mussolini as the residence of the Head of Government and of the Grand Council of Fascism.

Today the palace houses the museum with the same name. It is worth noting that the building incorporates the Basilica di S. Marco and in the corner between the Palazzo and the Palazzetto is one of the famous talking statues of Rome, “Madama Lucrezia”.