The little island in the far eastern end of Venice where this church was built was called Olivolo. It was first settled in the 5th and 6th Centuries, but 'settlement' likely meant just a few people, perhaps farmers. There was a church here early on, because every little settlement and neighborhood had its parish church. San Pietro di Castello was the seat of the bishop of Venice from the 9th century until 1451, when the Patriarchy was moved from Grado to Venice under Lorenzo Justinian's rule. That meant that San Pietro di Castello became the Cathedral of Venice. However, this particular building had not yet been built.

Palladio was commissioned by the Patriarch to design a new church building in 1559. The Patriarch died, and the work was interrupted. The facade was designed by Francesco Smeraldo in 1596. The facade resembles that of Palladio's Il Redentore church, on the Venetian island of Giudecca.