The history of Adana is intrinsically linked to the history of Tarsus; they seem often to be the same city, moving as the neighbouring Seyhan River changed its position, and the name changed too over the course of centuries. Adana was of little importance in ancient history, while Tarsus was the metropolis of the area. Also, Ayas (today Yumurtalık), and Kozan (formerly Sis) have been population and administrative centers, especially during the time of the Armenian Kingdom of Cilicia.
The history of Adana goes back more than 3000 years; finds in the region reveal human occupation of the area during the Paleolithic Age.
Tepebag Tumulus, where archaeologists found a stone wall and a city center, was built in the Neolithic Age; it is considered to be the oldest city of the Cilicia region.
An Adana is mentioned by name in a Sumerian epic, the Epic of Gilgamesh, but the geography of this work is too imprecise to identify its location.
According to the Hittite inscription of Kava, found in Hattusa (Boğazkale), Kizzuwatna was the first kingdom that ruled Adana, under the protection of the Hittites by 1335 BC. In that time, the name of the city was Uru Adaniyya, and the inhabitants were called Danuna.
Beginning with the collapse of the Hittite Empire, c. 1191-1189 BC, invasions from the west caused a number of small kingdoms to take control of the plain, as follows: Kue Assyrians, 9th century BC; Cilician Kingdom, Persians, 6th century BC; Alexander the Great in 333 BC; Seleucids; and the pirates of Cilicia and Roman statesman Pompey the Great.
During the era of Pompey, the city was used as a prison for the pirates of Cilicia. For several centuries thereafter, it was a waystation on a Roman military road leading to the East. After the split of the Roman Empire, the area became part of the Byzantine Empire, and was probably developed during the time of Julian. With the building of large bridges, roads, government buildings, and irrigation and plantation, Adana and Cilicia became the most developed and important trade centers of the region.