[10] The historical name of the town, al-Bīra in Arabic and Bīreh in Syriac, derives from the Aramaic Bīrthā, meaning fortress.

[11]: 159 The lowest geological layer in the Birecik area is the Gaziantep Formation, which dates to Eocene through Oligocene times.

[11]: 160  By this time, the Birecik area was no longer underwater – during the Middle and Late Miocene, tectonic activity had uplifted the region above sea level.

[15]: 54  Among the sites first identified by the Algaze survey were Akarçay Tepe and Mezraa Teleilat, which are two of the oldest known settlements in the Euphrates basin.

[15]: 54 The 1911 Encyclopædia Britannica identified Birecik with ancient Apamea[16] or its suburb Seleucia[17] and described it as opposite Zeugma, with which it was connected by a bridge of boats.

At the same time, it added that "the place seems to have had a pre-Seleucid existence as Birtha, a name which revived under Roman rule".

"[16] The placing of Apamea-Zeugma further upstream and the identification of Birecik with Roman Birtha was already stated in the American Journal of Archaeology in 1917;[20] and William Smith's Dictionary of Greek and Roman Geography (1854) clearly identified Birtha with Birecik, although at another point it seems to confuse it with "the Zeugma of Commagene",[10] the province on the right/west bank of the river.

[24]: 208  Al-bira had been under control by the Muslim Arabs from 637 until 1079 when it was conquered by the Seljuk Turk warlord Tutush but at some point afterwards it was taken by the Armenians.

[28] Matthew's account of this is suspect however as it seems that his daughter married the next lord, Galeran of Le Puiset of the Montlhery family, and it seems that Ablgharib's position was preserved to a certain extent.

[25] Birecik then formed part of the County of Edessa; it was strongly fortified with a castle and served as the capital of a minor feudal lordship.

[24]: 220  Birecik was unsuccessfully put under siege in 1420 by the Ak Koyunlu leader Kara Yusuf.

Again in 1472, the Ak Koyunlu leader Uzun Hasan attacked Birecik unsuccessfully, causing damage to the city walls.

[29] Meanwhile, by 1547 the Ottomans had chosen to make Birecik the site of a major imperial shipyard – the empire's first in Mesopotamia.

[29] Towns on the upper Tigris like Diyarbakır or Cizre would have therefore been less suitable for a large naval base compared to Birecik.

[29] At the same time, Birecik has a wetter climate than settlements further downstream because it's closer to the Mediterranean coast in Syria, and the mountain regions nearby are able to support large mixed-growth forests to supply timber for shipbuilding.

[29] The city of Basra, despite having the advantage of being much further downstream and closer to the Persian Gulf, has a drier climate and therefore lacked a consistent supply of wood.

[29] The Portuguese explorer Pedro Teixeira noted this problem when he visited Basra in 1604: since importing timber was costly, locally-built ships were small and expensive.

[29] The first reference to the Ottoman shipyard at Birecik is in June 1547, when an Arab merchant from Basra named Hajji Fayat reported to the Portuguese governor in Hormuz about it.

[29] Hajji Fayat specifically referred to the abundance of timber as one of the reasons why the "large and well-populated" town of Birecik was such an advantageous shipbuilding location.

[29] From October 1559 until February 1560, the Imperial Council wanted to build the ships at Birecik, but ultimately the vizier Sokullu Mehmed Pasha decided to send the materials to Basra instead and assemble the galliots there.

[29] Later, as part of an ultimately unsuccessful attempt to reconquer Baghdad in 1629, the Ottoman vizier Hüsrev Pasha ordered 100 new ships to be built at Birecik.

[16] Birecik Dam and hydroelectric power plant, part of the Southeastern Anatolia Project, is situated within the district.

With its rich architectural heritage, Birecik is a member of the Norwich-based European Association of Historic Towns and Regions (EAHTR) [30] There are 83 neighbourhoods in Birecik District:[31] In mid-19th century, Swiss traveler Alexander Schläfli recorded that Birejik had 5500-6000 people with 50-60 Armenian families and the rest being Turks.

[11]: 162  The exact source of the water is not known – locals believe it comes from Arat Dağı, but a survey by Gürpinar et al was unable to verify this.

[11]: 162  Gürpinar et al guessed that the ultimate source for the water is the karstic reservoir in the limestone member of the Gaziantep Formation.

[11]: 162  Its course is dug in a thick and relatively soft layer of rock that forms part of the Gaziantep Formation, and it stands without supports.

The Chronicle of Joshua the Stylite tells of a Bishop Sergius of Birtha who was entrusted by the Emperor Anastasius I Dicorus with refortifying the city, something that must have occurred after peace was made with the Persians in 504.