The Perugian statute of 1279, decreeing the expulsion of the Jews from the town, is proof that a Jewish settlement had previously been in existence in Perugia.

It seems, however, that this measure was never put into effect and in succeeding years there was an active Jewish group in Perugia, mostly engaged in moneylending.

The artist Matteo di Ser Cambio, who acted as “procurator” of the Jews of Perugia in 1414, illuminated a Hebrew manuscript there about this time.

The creation of the Monti di Pietá (1462), in conjunction with violent anti-Jewish preaching by the Franciscans, had dire consequences for the Jews in Perugia, and they were banished in 1485. Though later readmitted to the town, they were banished again in 1569 by the bull Hebraeorum Gens of Pius V. Under Sixtus V (1587) they returned temporarily, but in 1593 were banished finally by Clement VIII.

A few Jews graduated in medicine in the University of Perugia between 1547 and 1551, including David de’Pomis. In the 1920s and 1930s, many foreigners (including some from Ereẓ Israel) studied there, receiving moral support in the home of Bernard Dessau, the professor of physics and a father of wireless telegraphy, and his wife, the artist Emma Dessau.

There is again a handful of Jews living in Perugia, affiliated to the community of Rome, and services are held irregularly.