The town was originally known as '''Misiche''' (Greek: ), '''Mesiche''' (), or '''Massice''' ( mšyk;  mšyk). As a major crossing point of the Euphrates, and occupying the northernmost point of the complex irrigation network of the Sawad, the town was of considerable strategic significance. As the western gate to central Mesopotamia, it was fortified by the Sasanian ruler Shapur I () to shield his capital, Ctesiphon, from the Roman Empire. After his decisive defeat of the Roman emperor Gordian III at the Battle of Misiche in 244, Shapur renamed the town to '''Peroz-Shapur''' (''Pērōz-Šāpūr'' or ''Pērōz-Šābuhr'', from , meaning "victorious Shapur"; in ; in ). It became known as '''Pirisapora''' or '''Bersabora''' () to the Greeks and Romans.