There is no written evidence for earlier settlement at the site, but Urfa’s favorable commercial and geographical placement suggests that there was a smaller settlement present prior to 303 BC. The indigenous Aramaic name for the site prior to the Seleucid period was Orhai or Orhay, which survives as the basis of the city’s modern Turkish name.

Perhaps Orhai’s absence from earlier written sources is due to the settlement having been small and unfortified prior to the Seleucid period. Seleucus named the city after the ancient capital of Macedonia.

In the late 2nd century, as the Seleucid dynasty disintegrated, it became the capital of the Arab Nabataean Abgar dynasty, which was successively Parthian, Aramean/Syriac kingdom Osroene, Armenian, and Roman client state and eventually a Roman province. Its location on the eastern frontier of the Empire meant it was frequently conquered during periods when the Byzantine central government was weak, and for centuries, it was alternately conquered by Arab, Byzantine, Armenian, and Turkish rulers. In 1098, the Crusader Baldwin of Boulogne induced the final Armenian ruler to adopt him and then seized power, establishing the first Crusader State known as the County of Edessa and imposing Latin Christianity on the Greek Orthodox, Assyrian Church of the East and Armenian Apostolic majority of the population.

Urfa was conquered by Imad ad-Din Zangi in 1144 after a month-long siege, and from that point the city came under the Zengid dynasty. The last count of Edessa besieged the city again in 1146 in an attempt to retake it from the Zengids, but only held the city for six days before being defeated by Zangi’s son Nur ad-Din. Urfa’s population was massacred in the process, and its Christian community never recovered.

After the Zengids, Urfa was ruled by the Ayyubid dynasty from 1182 to 1260, when it was captured by the Mongols. In the early 1300s, it became part of the Mamluk Sultanate, and then the Aq Qoyunlu captured it in the early 1400s. The Ottoman Empire took Urfa around 1517 and ruled it until the 20th century. Under Ottoman rule, Urfa was initially made centre of Raqqa Eyalet, laterly part Urfa (Sanjak) of the Aleppo Vilayet. The area became a centre of trade in cotton, leather, and jewellery.