This church is the seat of the Mantua bishop and was originally constructed during the Early, Christian era, but it was burnt in 894. The only artifact that remains from that period is the bell tower basement. There is some belief that the basement was originally a Roman tower constructed on an Etruscan foundation. A Roman statue head is present above the windows of the bell tower.

The current church was constructed during the 14th-century in Romanesque style. The structure was enlarged during this time in late Gothic architecture. The church was restored again in 1545 by Giulio Romano, who rebuilt only the interior, which was copied from the old Saint Peter's Basilica in Rome.

The last change occurred between 1756-1761 when a Baroque facade was added to the church. Many of these artistic styles are still visible today.