The Cannaregio Canal, which was the main route into the city until the construction of a railway link to the mainland, gave the district its name (Canal Regio is Italian for Royal Canal). Development began in the eleventh century as the area was drained and parallel canals were dredged.

Although elegant palazzos were built facing the Grand Canal, the area grew primarily with working class housing and manufacturing.

Beginning in 1516, Jews were restricted to living in theVenetian Ghetto.

It was enclosed by guarded gates and no one was allowed to leave from sunset to dawn. However, Jews held successful positions in the city such as merchants, physicians, money lenders, and other trades. Restrictions on daily Jewish life continued for more than 270 years, until Napoleon Bonaparte conquered the Venetian Republic in 1797.

He removed the gates and gave all residents the freedom to live where they chose.