The ancient Perusia, now Perugia, first appears in history as one of the twelve confederate cities of Etruria. It is first mentioned in the account of the war of 310 or 309 BC between the Etruscans and the Romans. It took, however, an important part in the rebellion of 295, and was reduced, with Vulsinii and Arretium (Arezzo), to seek for peace in the following year.

In 216 and 205 it assisted Rome in the Hannibalic war, but afterwards it is not mentioned until 41-40 BC, when Lucius Antonius took refuge there, and was reduced by Octavian after a long siege. A number of lead bullets used by slingers have been found in and around the city (CIL xi. 1212). The city was burnt, we are told, with the exception of the temples of Vulcan and Juno — the massive Etruscan terrace-walls, naturally, can hardly have suffered at all — and the town, with the territory for a mile round, was allowed to be occupied by whoever chose. It must have been rebuilt almost at once, for several bases exist, inscribed Augusta sacr(um) Perusia restituta; but, as we have seen, it did not become a colony until AD 251-253.