The building is the seat of a confraternity established in 1478, named after San Rocco, popularly regarded as a protector against plague.[1] The members of the "Confraternity of St. Roch" were a group of wealthy Venetian citizens. The site they chose for their building is next to the church of San Rocco which houses the remains of the saint.

In January 1515 the project of the building was entrusted to Bartolomeo Bon, although some authorities assign it to his son Pietro Bon. In 1524 his work was continued by Sante Lombardo, who, in turn, three years later was replaced by Antonio Scarpagnino. Following his death in 1549, the last architect to work on the edifice was Giangiacomo dei Grigi, finishing in September 1560.[2]

The design was similar to other scuole in Venice, characterized by two halls, one at ground floor level, the other at first floor level. The Sala Terra (lower) has a nave and two aisles, with the entrance from the campo[3] outside. From this hall a stair (with a landing surmounted by a dome) led to the upper storey. The Sala Superiore ("Upper Hall") was used for meetings of the fellows and had a wooden altar. It provided access to the Sala dell'Albergo, which housed the Banca and the Zonta (the confraternity's supervisory boards).