While racial and ethnic neighborhoods had existed prior to the Venetian Ghetto, Venice's ghetto was the first "ghetto" (coming from a Venetian word for the Iron Foundry that had been on the site) and "ghetto" eventually came to mean any neighborhood that was made up of a single ethnic/racial group. Today, Jewish life is still very active in the ghetto, and elsewhere in Venice, and is home to five synagogues. Visiting on Saturdays or late Fridays (the Jewish Sabbath) will prove very fruitless because all shops, restaurants, and other Jewish places will be closed.

The Venetian Ghetto (Venetian: Gheto de Venesia) was the area of Venice in which Jews were forced to live by the government of the Venetian Republic. The English word ghetto is derived from the Jewish ghetto in Venice. The Venetian Ghetto was instituted on 29 March 1516 by decree of Doge Leonardo Loredan and the Venetian Senate. It was not the first time that Jews in Venice were compelled to live in a segregated area of the city. In 1555, Venice had 160,208 inhabitants, including 923 Jews, who were mainly merchants.

Between 1541 and 1633, the Ghetto Vecchio ("Old Ghetto") and Ghetto Nuovo ("New Ghetto") were made to accommodate the increase in Jewish immigration, but the total number of Jews in Italy did not exceed 25,000. The Jewish community in Venice did not exceed 5,000 until the early seventeenth century.

In 1797, the French Army of Italy, commanded by the 28-year-old General Napoleon Bonaparte, occupied Venice, forced the Venetian Republic to dissolve itself on 12 May 1797, and ended the ghetto's separation from the city on 11 July of the same year. In the 19th century, the ghetto was renamed the Contrada dell'unione.