In antiquity, this region bordered the Armenian provinces of Tsopk and Aghdznik to the North, as well as Assyrian Mesopotamia and Commagene to its south.

[1] For most of its history, Armenian Mesopotamia was primarily composed of the major cities of Diyarbakir (Amid), Tigranocerta, Dara, Tur Abdin (Cephas), Dadima, Arsamosata, and Citharizum.

[5] Historically, the borders of Armenia extended to Mesopotamia and a large number of Armenian merchants and artisans migrated there during the Achaemenid and Seleucid periods.

Even after the region was retaken by the Romans, significant Mesopotamian Armenian communities continued to exist, especially in the cities of Antioch, Amida, and Edessa.

[5] A large number of Armenians moved to northern Mesopotamia following the conquest of the Bagratid Kingdom of Armenia by the Byzantine Empire in the 11th century AD.