Set up in 1923 to commemorate the 400th anniversary of the death of Pietro Perugino, it was reopened in 2000 with a new layout that winds through 25 rooms on two floors, through the suggestive remains of Palazzo di Martino IV, Palazzo dei Consoli, and Palazzo del Capitolo dei Canonici. In the subterranean vault is a stone tablet related to Perugia’s urban layout in Etruscan-Roman times.

Displaying works of art and religious decorations from churches all over the diocese and from the cathedral, as well as donations, it preserves numerous paintings and sculptures from the 14th century to 19th century, including works from the workshops of Arnolfo di Cambio and Agnolo Daddi, and others by Meo da Siena, Giannicola di Paolo and Bartolomeo Caporali. Early mannerism and the 17th century are represented by the work of Danti, Scaramuccia and Batini. Particularly noteworthy is the Altarpiece of Sant’Onofrio by Luca Signorelli (1484), portraying the enthroned Madonna and Child, an angel playing an instrument, and at the sides John the Baptist and the saints Onofrio and Lorenzo together with the commissioning party.