Set near the Syrian border, Kilis is where the Mediterranean Region transitions into the South East Anatolia Region. The city and its surrounding area have been inhabited uninterruptedly since the Neolithic Age – the beginning of human settlement and cultivation of the land. Numerous civilizations have found a home here, including the Babylonians, the Hittites (Kilis was an important city of the Hittite State in BCE 1700) and the Hurri-Mitanni. The Aramaic, Assyrian, Med, Pers, Macedonian, Roman, Byzantine, Muslim Arab (The four caliphs, Umayyad, Abbasi), Seljuk, Memluk (Kolemen) and Ottoman empires were also present in and around Kilis.
The name, Kilis, was also borne by an ancient city in Upper Mesopotamia called Pellada Cyrrhus. The area where the city centre is located today was referred to as Kilis Castle (Kilis Kalesi) in Ottoman sources.