A parish church stood at the site since the 11th century, patronized by the patrician Dandolo and Pizzamano families.

In the altar in the presbytery is an altarpiece depicting The Virgin appears to St. Luke as he writes the Gospel by Paolo Veronese.

In the right lateral chapel is an altarpiece of Virgin and Saints by Palma il Giovane.

In the second altar to the left, is a painting depicting Lorenzo Giustiniani, first Patriarch of Venice, defeating the plague and distributing alms by Carlo Loth.

Pietro Aretino, Lodovico Dolce, and other men of letters are buried in San Luca.