Little is known of the region of Commagene prior to the beginning of the 2nd century BC. However, it seems that, from what little evidence remains, Commagene formed part of a larger state that also included the Kingdom of Sophene. The later kings of Commagene claimed descent from the Orontid Dynasty and would therefore have been related to the family that founded the Kingdom of Armenia. The accuracy of these claims, however, is uncertain.
This control lasted until c.163 BC, when the local satrap, Ptolemaeus of Commagene, established himself as independent ruler following the death of the Seleucid king, Antiochus IV Epiphanes. The Kingdom of Commagene maintained its independence until 17 AD, when it was made a Roman province by Emperor Tiberius. It reemerged 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 reemergent state lasted until 72 AD, when the Emperor Vespasian finally and definitively made it a part of the Roman Empire.
Commagene was a small kingdom, located in modern south-central Turkey, with its capital at Samosata (modern Samsat, near the Euphrates). It was first mentioned in Assyrian texts as Kummuhu, which was normally an ally of Assyria, but eventually annexed as a province in 708 BC under Sargon II. The Achaemenid Empire then conquered Commagene in the 6th century BC and Alexander the Great conquered the territory in the 4th century BC. After the breakup of the Alexandrian Empire, Commagene was a state and province in the Greco-Syrian Seleucid Empire.
The Hellenistic kingdom of Commagene, bounded by Cilicia on the west and Cappadocia on the north, arose in 162 BC. This was the year when its governor, Ptolemy, a satrap of the disintegrating Seleucid Empire, declared himself independent. Ptolemy's dynasty was related to the Parthian kings, but his descendant Mithridates I Callinicus (109 BC–70 BC) embraced the Hellenistic culture and married the Syrian Greek Princess Laodice VII Thea. His dynasty could thus claim ties with both Alexander the Great and the Persian kings. This marriage may also have been part of a peace alliance between Commagene and the Seleucid Empire. From this point on, the kingdom of Commagene became more Greek than Persian.
Mithridates and Laodice’s son was King Antiochus I Theos of Commagene (reigned 70 BC–38 BC). Antiochus was an ally to Roman general Pompey in his campaigns against Mithridates VI of Pontus in 64 BC. Through skilled diplomacy, Antiochus was able to keep Commagene independent from the Romans. In 17 when Antiochus III of Commagene died, Emperor Tiberius annexed Commagene to the province of Syria, but in 38 Caligula reinstated his son Antiochus IV and also gave him the wild areas of Cilicia to govern. Antiochus IV was the only Client King of Commagene under the Roman Empire. Antiochus IV reigned until 72, when Emperor Vespasian deposed the dynasty and re-annexed the territory to Syria, acting on allegations "that Antiochus was about to revolt from the Romans... reported by the Governor Caesennius Paetus". The descendants of Antiochus IV lived prosperously and in distinction in Anatolia, Greece, Italy and the Middle East. As a testament to the descendants of Antiochus IV, was his grandson Philopappos who died in 116. The citizens of Athens in 116, erected a funeral monument in honour of Philopappos, who was a benefactor of Athens. Another descendant of Antiochus IV was the historian Gaius Asinius Quadratus, who lived in the 3rd century.
When the Romans conquered Commagene, the great royal sanctuary at Mount Nemrut was abandoned. The Romans looted the burial tumuli of their goods and the XVI legion (Legio XVI Flavia Firma) built and dedicated a bridge. The surrounding thick forests were cut down and cleared by the Romans for wood, timber and charcoal, causing much erosion to the area. In Commagene, there is a column topped by an eagle, which has earned the mound name Karakush, or Black Bird. An inscription there indicates the presence of a royal tomb that housed three women. The vault of that tomb, however, has also been looted. The main excavations on the site were carried out by Friedrich Karl Dörner of the University of Münster.