It was founded near the end of the 4th century BC by Seleucus I Nicator , one of Alexander the Great 's generals . Antioch became a rival of Alexandria as the chief city of the nearer East and the cradle of gentile Christianity . Founded near the end of the 4th century BC by Seleucus I Nicator , one of Alexander the Great 's generals , Antioch eventually rivaled Alexandria as the chief city of the Near East and was a cradle of Gentile Christianity .