The Roman conquest marks the end of Epirus' political independence.

In 146 BCE, Epirus becomes part of the province of Roman Macedonia, receiving the name Epirus vetus ("Old Epirus"), to distinguish it from Epirus nova ("New Epirus") to the north.

Its coastal regions grow wealthy from the Roman coastal trade routes, and the construction of the Via Egnatia provides a further boost to prosperity.

When the Roman Empire is divided in two in 395, Epirus becomes part of the Eastern Roman Empire (subsequently the Greek-speaking Byzantine Empire), ruled from Constantinople.