The territory around Modena (Roman Mutina, Etruscan Muoina) was inhabited by the Villanovans in the Iron Age, and later by Ligurian tribes, Etruscans, and the Gaulish Boii (the settlement itself being Etruscan).

Although the exact date of its foundation is unknown, it is known that it was already in existence in the third century BCE, for in 218 BCE, during Hannibal's invasion of Italy, the Boii revolted and laid siege to the city.

Livy described it as a fortified citadel where Roman magistrates took shelter.

The outcome of the siege is not known, but the city was most likely abandoned after Hannibal's arrival.

Mutina is refounded as a Roman colony in 183 BCE, to be used as a military base by Marcus Aemilius Lepidus.