In 810, Doge Agnello Participazio moved the seat of government from the island of Malamocco to the area of the present-day Rialto, when it was decided a palatium duci (Latin for "ducal palace") should be built. However, no trace remains of that 9th-century building as the palace was partially destroyed in the 10th century by a fire. The following reconstruction works were undertaken at the behest of Doge Sebastiano Ziani (1172–1178). A great reformer, he would drastically change the entire layout of the St. Mark's Square. The new palace was built out of fortresses, one façade to the Piazzetta, the other overlooking the St. Mark's Basin. Although only few traces remain of that palace, some Byzantine-Venetian architecture characteristics can still be seen at the ground floor, with the wall base in Istrian stone and some herring-bone pattern brick paving.
Political changes in the mid-13th century led to the need to re-think the palace's structure due to the considerable increase in the number of the Great Council's members. The new Gothic palace's constructions started around 1340, focusing mostly on the side of the building facing the lagoon. Only in 1424 did Doge Francesco Foscari decide to extend the rebuilding works to the wing overlooking the Piazzetta, serving as law-courts, and with a ground floor arcade on the outside, open first floor loggias running along the façade, and the internal courtyard side of the wing, completed with the construction of the Porta della Carta (1442).
In 1483, a violent fire broke out in the side of the palace overlooking the canal, where the Doge's Apartments were. Once again, an important reconstruction became necessary and was commissioned from Antonio Rizzo, who would introduce the new Renaissance language to the building's architecture. An entire new structure was raised alongside the canal, stretching from the ponte della Canonica to the Ponte della Paglia, with the official rooms of the government decorated with works commissioned from Vittore Carpaccio, Giorgione, Alvise Vivarini and Giovanni Bellini.
Another huge fire in 1547 destroyed some of the rooms on the second floor, but fortunately without undermining the structure as a whole. Refurbishment works were being held at the palace when in 1577 a third fire destroyed the Scrutinio Room and the Great Council Chamber, together with works by Gentile da Fabriano, Pisanello, Alvise Vivarini, Vittore Carpaccio, Giovanni Bellini, Pordenone, and Titian. In the subsequent rebuilding work it was decided to respect the original Gothic style, despite the submission of a neo-classical alternative designs by the influential Renaissance architect Andrea Palladio. However, there are some classical features — for example, since the 16th century, the palace has been linked to the prison by the Bridge of Sighs.
As well as being the ducal residence, the palace housed political institutions of the Republic of Venice until the Napoleonic occupation of the city in 1797, when its role inevitably changed. Venice was subjected first to French rule, then to Austrian, and finally in 1866 it became part of Italy. Over this period, the palace was occupied by various administrative offices as well as housing the Biblioteca Marciana and other important cultural institutions within the city.
By the end of the 19th century, the structure was showing clear signs of decay, and the Italian government set aside significant funds for its restoration and all public offices were moved elsewhere, with the exception of the State Office for the protection of historical Monuments, which is still housed at the palace's loggia floor. In 1923, the Italian State, owner of the building, entrusted the management to the Venetian municipality to be run as a museum. Since 1996, the Doge’s Palace has been part of the Venetian museums network, which has been under the management of the Fondazione Musei Civici di Venezia since 2008.