The prehistory of Mesopotamia, spanning from the Paleolithic to the advent of writing in the Fertile Crescent region, encompasses the Tigris and Euphrates rivers, Zagros foothills, southeastern Anatolia, and northwestern Syria. This period is not well-documented, especially in southern Mesopotamia before the 4th millennium BCE, due to geological conditions burying remains under alluvium or submerging them in the Persian Gulf.

In the Middle Paleolithic, hunter-gatherers inhabited the Zagros caves and open-air sites, producing Mousterian lithic tools. Notably, Shanidar Cave's funerary remains reveal practices of solidarity and healing within these groups.

The Upper Paleolithic era saw modern humans in the Zagros region, using bone and antler tools, identified as part of the local Aurignacian culture, known as "Baradostian".

The late Epipaleolithic period, around 17,000-12,000 BCE, is marked by the Zarzian culture and the emergence of temporary villages with circular structures. The use of fixed objects like millstones and pestles indicates the beginning of sedentarization.

Between the 11th and 10th millennia BCE, the first villages of sedentary hunter-gatherers appeared in northern Iraq. These settlements featured houses built around a central "hearth", suggesting a form of family property. Evidence of skull preservation and artistic depictions of birds of prey has been found, highlighting cultural practices of this era.