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Digs at the tell (artificial mound) to the south of the centre of the modern city indicate there were settlements in preclassical times. However, Homs only gained importance during the Roman era. Formerly known as Emesa, the town benefited from close ties with Palmyra, 125km to the east.

Its regional importance was further enhanced around AD 187, when Julia Domna, daughter of an Emesan high priest, married a Roman garrison commander, Septimius Severus, who six years later would become emperor of Rome. They founded a Syro-Roman dynasty that spanned four emperors (reigning from 211 to 235). Unfortunately it was a dynasty most noted for its rapid decline into depravity. Most notorious of all was Elagabalus, whose four-year reign of chaos was abruptly terminated when he was assassinated by his own Praetorian guards, seeking to restore some order to the empire.

Under the Byzantines, Homs became an important centre of Christianity, and it still has a very large Christian population. After falling to a Muslim army led by the general Khaled ibn al-Walid (revered as the warrior who brought Islam to Syria) in 636, Homs became an equally fervent centre of Islam.