Dorsoduro includes the highest land areas of the city as well as the islands of Giudecca and Sacca Fisola. The name "Dorsoduro" derives from the Italian for "hard ridge", due to its comparatively high, stable land.

The original heart of the area was the Giudecca Canal, along which buildings were constructed beginning in the sixth century. By the eleventh century, settlements had spread across to the Grand Canal, while later religious buildings including the Basilica of Santa Maria della Salute and the Zattere quay are now its main landmarks.

The western part of this sestiere is comprised of the Island of Mendigola, which was one of the first colonized areas of Venice, some centuries before the Rialto became the vital centre of Venice. In the eleventh century, the important Church of San Nicolò dei Mendicoli was built on this island. The near islands were colonized after, until finally reaching Customs Point (the Punta della Dogana), which is named in fact as the original Customs Point of Venice. The last marshland to be filled was the area that extends from the Customs Point to the monastery, where now stands the Basilica of Santa Maria della Salute.

In the nineteenth century, the Accademia was founded in Dorsoduro and the Accademia Bridge linked this sestiere to St. Mark, making it an expensive area popular with foreign residents. The western quarter, the point and the Giudecca all became industrialised around this time.

Attractions on the main islands include the Peggy Guggenheim Collection, the Palazzo Dario, San Trovaso, San Pantalon, San Nicolò dei Mendicoli, the Church of San Sebastiano, the Palazzo Ariani, the Palazzo Zenobio, the Church of Santa Maria del Carmelo and the Great School of Carmini, Campo Santa Margherita, Ca' Foscari and Ca' Rezzonico.