Zeugma was founded in the early 3rd century BC as the city of Seleucia by Seleucus I Nicator, a Diadochus (successor) to Alexander the Great and Macedonian founder of the Seleucid Kingdom, on the site where he had the first bridge over the Euphrates built.

Up to 70,000 people lived in the city, and it became a center for the military and commerce for the ancient Romans.

[3] In late antiquity, Zeugma was a diocese of the early Roman church, but the place seems to have been abandoned in the 7th century due to Sassanid Persian and then Arab raids by the Umayyad Caliphate.

[5] After reading about it in The New York Times, and with only few months left, American philanthropist David W. Packard donated USD 5 million to fund an emergency excavation of the archaeological site, allowing archaeologists to preserve the mosaics that would otherwise be inundated by the dam.

[10] The Zeugma Mosaic Museum attracted a record 340,569 visitors in 2019, according to the Turkish Culture and Tourism Ministry.