Founded in the 10th century, the church was the cathedral of Assisi before 1036, when the church of San Rufino took over the position.

The building we see today dates back to the 12th century. The simple facade bears an inscription from 1163 and is divided into three sections by pilaster strips.

The nave, semi-circular apse and sacristy still have remains of frescoes from the 14th and 15th century. A late-Medieval 9th century sarcophagus lies to the right of the entrance. The crypt dates back to the previous church and leads via a passageway to the so-called House of Propertius, with its Pompeian style wall paintings. Remains of the old Roman city walls are visible from the adjacent gardens.

Built out of limestone from Mount Subasio, the Roman blocks have been used as a base for the later Medieval fortifications.

Although Santa Maria Maggiore had lost its status of cathedral, the nearby bishop's palace where St Francis renounced his earthly wealth continued to be used as such.