Most likely of Hittite origin, it was incorported into the Assyrian Empire in 708 BC. Later it served as the capital for the Hellenistic kingdom of Commagene from circa 160 BC until it was surrendered to Rome in 72 CE.
Samosata was the birthplace of Lucian (c. 120-192 CE), a famous writer of antiquity, who is said to have written the first space novel, as well as 80 works which have survived to this day.
Samosata was also the birthplace of Paul, the third leader of the Elkasites, an order of Essene Gnostics, who lived during the middle of the third Century of the Common Era.
Seven Christian martyrs were crucified in 297 in Samosata for refusing to perform a pagan rite in celebration of the victory of Emporer Maximian over the Persians. Those crucified were Abibus, Hipparchus, James, Lollian, Paragnus, Philotheus, and Romanus.
It was at Samosata that Julian had ships made in his expedition against Sapor, and it was a natural crossing-place in the struggle between Heraclius and Chosroes in the 7th century.
In February, 1098, the emir Baldoukh, attacked by Baudouin of Antioch, cut his army to pieces there. In 1114 it was one of the chief quarters of the Muslims hostile to the Count of Edessa, to whom it succumbed, but was recaptured by the Mussulmans about 1149.