Commagene was an ancient Greco-Iranian kingdom ruled by a Hellenized branch of the Iranian Orontid dynasty that had ruled over Armenia. The kingdom was located in and around the ancient city of Samosata, which served as its capital. The Iron Age name of Samosata, Kummuh, probably gives its name to Commagene.

Commagene has been characterized as a "buffer state" between Armenia, Parthia, Syria, and Rome; culturally, it was correspondingly mixed. The kings of the Kingdom of Commagene claimed descent from Orontes with Darius I of Persia as their ancestor, by his marriage to Rhodogune, daughter of Artaxerxes II who had a family descent from king Darius I. The territory of Commagene corresponded roughly to the modern Turkish provinces of Adıyaman and northern Antep.

Little is known of the region of Commagene prior to the beginning of the 2nd century BCE. However, it seems that, from what little evidence remains, Commagene formed part of a larger state that also included the Kingdom of Sophene. This situation lasted until c. 163 BCE, when the local satrap, Ptolemaeus of Commagene, established himself as an independent ruler following the death of the Seleucid king, Antiochus IV Epiphanes.

The Kingdom of Commagene maintained its independence until 17 CE, when it was made a Roman province by Emperor Tiberius. It re-emerged as an independent kingdom when Antiochus IV of Commagene was reinstated to the throne by order of Caligula, then deprived of it by that same emperor, then restored to it a couple of years later by his successor, Claudius. The re-emergent state lasted until 72 CE, when the Emperor Vespasian finally and definitively made it part of the Roman Empire.