In 1516, the Senate of the Republic of Venice passed a law obliging all Jews of the city to settle on an island east of San Girolamo. At the two bridges, which connected the island with the rest of the city, gates were attached and at night guards posted. "The ghetto walls, a concrete, physical barrier, suddenly became a powerful and penetrating sign," a booklet from the Museo ebraico summarizes the effect of the edict of 1516.
In order to create more apartments on the island of the ghetto, the buildings were raised to eight floors. In 1541, the area of the ghetto was extended and the streets of the so-called Ghetto Vecchio ("Old Ghetto") added to the west; In 1633, the ghetto Novissimo ("Newest Ghetto") was added, a small area east of Ghetto Nuovo, only two streets wide.
In the southern part of the large square in the center of the historic ghetto, at the Campo del Ghetto Nuovo, there is now the Jewish Museum, which is open every day except on the Sabbath and on Jewish holidays . In addition to a permanent exhibition, the museum also offers guided tours of the historic ghetto and two of the five neighboring synagogues. The reliefs of the Lithuanian sculptor Arbit Blatas on the Campo del Ghetto Nuovo are reminiscent of the Venetian Jews deported and murdered under German occupation from 1943 onwards.