Perugia’s as well as Umbria’s largest church (96 m long, 30 m wide between the naves and 60 m in the transept, 30 m high), it was built in two phases between 1304 and 1458, taking up a consistent portion of the district and of the ancient parish of Santo Stefano del Castellare. Reconstructed by Carlo Maderno (1632) after a succession of collapses, it holds especially interesting garrets hidden above its vaults (visible on request). Inside is the lovely funereal monument to Pope Benedict XI, who died in Perugia on July 7, 1304, of the Tuscan school (14th cent.), as well as frescoes attributed to Cola Petruccioli and Allegretto Nuzi (14th cent.), the altar piece by Agostino di Duccio (1459), the gonfalon by Giannicola di Paolo (1494), a 16th century wooden chorus and a 17th century organ. The large apsidal window, 23 m high, was created by the artists Bartolomeo di Pietro of Perugia and Mariotto di Nardo of Florence in 1411. Many of the artistic works it held are now on display at the National Gallery of Umbria, such as the Polyptych of the Dominicans or the Guidalotti Polyptych by Beato Angelico.

The bell tower was erected by the Lombard architect Gasperino di Antonio in the 15th century, it features two orders of large gothic windows once decorated with marble lacing, of which only one remains, reconstructed in 1949 using original materials. The very tall spire thick with statues was demolished in the period of construction of the Rocca Paolina (1540-43).