In all periods the region of Cilicia was of strategic importance for the connection between Syria and the Northern Levant – and thus also including Mesopotamia and Egypt –, Cyprus and Central Anatolia.

This is also exemplified by the archaeological material discovered: in the early Chalcolithic period (ca. 5000 BC) certain pottery types found in Cilicia seem to reflect both Northern Mesopotamian and Central Anatolian features. Cultural influences of the Mesopotamian Halaf period and the following ́Ubaid period are attested in Cilicia as well. In these periods an especially intense contact also seems to have existed with the neighboring ́Amuq Plain ( ́Amuq E and F) which is separated from Cilicia by the Amanus Mountains.

The first written reference to Cilicia may come from Egypt and date to the first quarter of the second millennium BC: here, a country called »Kawa« is apparently mentioned. Around the end of the Middle Bronze Age (ca. 1600 BC) the Hurrian Language and Religion spread out in Cilicia and mingled with the local Luwian language, an Indo-European language which is related to the Hittite language.

This period was greatly affected by the existence of the Kingdom of Kizzuwatna which was formed around the middle of the second millennium BC. Kizzuwatna remained an independent and autonomous kingdom between the Hittites and Mittani until it was incorporated into the Hittite Kingdom around 1350 BC. A number of kings of Kizzuwatna are attested.

The political and historical role and the influence that Kizzuwatna had on the Hittites was important and not to be underestimated: the country gave fast and easy access to Syria, thus helping the Hittites to intensify trade and also giving strategic political advantages. Culturally, the Kingdom of Kizzuwatna with its Hurrian and Luwian populations and the direct connection to Syria exerted strong influence on the Hittite culture, especially in religious aspects.

After the decline of the Late Bronze Age world its and cultural sphere also the region of Kizzuwatna broke apart. In the early first millennium BC two smaller kingdoms seem to emerge: Hilakku in the Tauros Mountains north of Adanija (modern Adana) and Que (Qawa) in Flat Cilicia which both had contacts and relations with other Late Hittite kingdoms such as Tabal (north of the Tauros Mountains) and Northern Syria. Both territories were under strong Assyrian influence and later became provinces of the Assyrian Empire.

The inscriptions of Azatiwada – at that time protector of the later King Awarik – from Karatepe (Azatiwataya), dating to the early 8th century BC, mention a kingdom of » ́mq ́dn« (the »Plain of Adana«) and Awarik as »mlk dnnym« (»King of Danunians«) of the house of »bt mps« (the »House of Mopsos«). This Mopsos (Phoenician »MPŠ«, Luwian »Muksa«) who – according to Greek historical tradition – is said to have been ruling in Pamphylia and Cilicia in the 12th century BC, could have been a late ruler of Tarhuntašša. Furthermore, in Flat Cilicia a number of sites are named after him (e.g. »Mopsuhestia«). In his slightly later inscription on the statue found at Çineköy, the afore mentioned King Awarik/Warikas (Assyrian »Urikki«, »Urik«), a contemporary of the Assyrian King Tiglat-Pileser III, calls his country Hiyawa. This toponym is most probably to be ethymologically associated with the Assyrian forms of Qawe/Quwe/Que and the neo-Babylonian Hume.

Also, if King Awarik is identical with the King »Urikku« mentioned in the inscription of Pihala ́as (=Pellas) at Cebelires Dağı, even the region of Alanya would have been under Que ́s domination. Que was under strong Assyrian influence since King Tiglat-Pileser III (ca. 744–727 BC) and most probably became a province of the Assyrian Empire under Shalmaneser V (726-722 BC). Despite some occasional rebellions it remained a province of the Assyrian and Babylonian Empires. During the Achaemenid Empire the region of Que was unified to one with the western region of Hilakku (Silifke/Seleukia, the region that was later to become »Rugged Cilicia«) under the Dynasty of the Syènnesis (=Luwian »suwanassa«: »belonging to the dog«). Because of this, presumably, the appellation »Cilicia« (Hilakku) was given to both regions since then.

In Hellenistic times Cilicia was torn between by the Seleucid and Lagid Empires: after Alexander’s death it was long a battleground of rival Hellenistic marshals and kingdoms, and for a time fell under Ptolemaic dominion (i.e. Egypt), but finally under that of the Seleucids, who, however, never held effectually more than the eastern half of Cilicia. The cities newly founded or re-established were Seleukia/Kalykadnos (ancient Ura?), Aigéai and Arsinoe. Cilicia Trachea (»Rugged Cilicia«) became the haunt of pirates, who were subdued by Pompey in 67 BC following a battle at Korakesion (modern Alanya), and Tarsus was made the capital of the Roman province of Cilicia. The region of »Flat Cilicia« became a Roman province which at first was ruled and administrated by a local regent called Tarkondimotos. In 50/51 AD, famous Roman politician, statesman and philosopher Marcus Tullius Cicero was governor (proconsul) of the province with his seat at Tarsus.

Later, the province of Cilicia was governed by the Byzantine Empire. In the 7th century it was invaded and ruled by the Caliphates of the Umayyads and Abbasids, who held the country until it was reoccupied by the Byzantine emperor Nicephorus II in 965 AD. In the Middle Ages the Armenian Kingdom of Cilicia was formed which was independent from around 1078 to 1375.