Cilicia was annexed to the Roman Republic in 64 BC by Pompey, as a consequence of his victory over the Cilician pirates and in the Third Mithridatic War.

In 96 BC, Lucius Cornelius Sulla was appointed the propraetorial governor of Cilicia, during which time he stopped an invasion by Mithridates II of Parthia.

[4] Then in 75 BC Vatia Isauricus advanced across a Roman army across the Taurus Mountains for the first time, and succeeded in defeating the Isauri along the northern slopes.

To the east of Cilicia Campestris, Pompey left a local dynast, Tarcondimotus I, in control of Anazarbos and Mount Amanus.

Further changes were made by Marcus Antonius in 36 BC, when he gave Cyprus and Cilicia Aspera to Cleopatra VII, and eastern Phrygia with Lycaonia, Isauria, and Pisidia, to king Amyntas of Galatia.

As per the late Republican and early imperial methods of provincial rule, the western mountainous parts of Cilicia, which were not easy for a governor to manage, were left to the native princes.

The son of Tarcondimotos in eastern Cilicia had lost his throne in 30 BC because of his father's unwavering support of Mark Antony, but the kingdom was restored in 20 BC; it was to last another 37 years before Tiberius finally abolished this client kingdom and changed it to a full province.

In 72 AD, during the reign of Vespasian, all three remaining client kingdoms established by Augustus were disestablished, and merged with the imperial province of Cilicia.

These 3 Cilician provinces, plus the Syrian, Mesopotamian, Egyptian and Libyan provinces, formed the Diocese of the East (in the late 4th century the African component was split off as Diocese of Egypt), part of the praetorian prefecture of the East, the rich bulk of the eastern Roman Empire.

The status quo would remain unchanged for over 260 years before Cilicia was eventually reconquered for the Romans in the 950s and 960s by Nikephoros Phokas and John Tzimiskes.