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The Confraternity of St. Roch stands next to the Church of San Rocco, like other structures in the city it was built as a response to a plague which overtook the city in 1478. A confraternity is a group of Roman Catholic laymen who work towards promoting Christian charity. The organization gained importance in 1485 when they came into possession of the relics of St. Roch's body. The group raised money and had the Church of St. Roch built and next to it a building for their organization's activities in 1489 and 1508. The building was rebuilt on a grander scale in 1517 and designed by Bartolomeo Bon. In 1524 Bon was followed by Sante Lombardo and several years later by Antonio Abbondi (Scarpagnino) took over. Tintoretto is responsible for the church's lavish interior which took shape from 1564 to 1587.

The Scuola has three main rooms, a large space with grand columns on the entrance level (Sala Inferiore), connected to a similar room on the second floor (Sala Superiore) by a staircase with the landing topped by a dome. The second floor hall has a wooden altar and leads onto the Sala dell'Albergo or boardroom. Tintoretto created almost all the art work in the building and he offered the many paintings on canvas for free as a sign of his faith. The canvases cover the ceilings and walls like frescoes. Other works of art include paintings by Titian and Palma the Younger.

The Scuola is attached to the San Rocco Church which was based on a design by Bon. The church has a single aisle with two side chapels and the façade has three sections divided by tall pilasters.