In 113, the Roman emperor Trajan launched a war against Rome's long-time eastern rival, the Parthian Empire. By 114, he conquered Armenia and made it into a province. The end of 115 saw him conquer northern Mesopotamia. This territory was organized as a province in early 116 when coins were minted to celebrate the achievement. Later that same year, Trajan marched into central and southern Mesopotamia. He enlarged the province and completed its boundaries across the river Tigris to Adiabene. He annexed this region into another Roman province called Assyria. In the last months of 116, he captured the Persian city of Susa. He deposed the Parthian king Osroes I and placed his own puppet ruler Parthamaspates on the throne. Never again would the Roman Empire advance so far to the east.
Severus Reorganization
Northern Mesopotamia came under Roman control again during the expedition of Lucius Verus between 161 and 166. These lands were not formally organized into provinces but left under local vassal rulers. Roman garrisons remained at Nisibis. Control faced threats in 195 during civil war between Septimius Severus and the usurper Pescennius Niger. Rebellions broke out in the area while Nisibis was besieged. Severus quickly restored order and organized Osroene as a full province. Next, Severus embarked on a war against Parthia which he concluded successfully with the sack of the Parthian capital Ctesiphon. In emulation of Trajan, he re-established a province of Mesopotamia in 198. Nisibis was elevated to the status of a full colonia and became its capital. Unlike Trajan's province, this new territory was limited between Osroene to the south and the Euphrates and Tigris rivers to the north. The river Chaboras marked the eastern boundary.Roman Sassanian Border Wars
For the remainder of its existence, the province would remain a bone of contention between Romans and their eastern neighbors. It suffered heavily in recurrent Roman, Persian Wars. In the turmoil following the Year of the Six Emperors, Ardashir I attacked and overran the area between 239 and 243. He founded the new Sassanid Empire which replaced the moribund Parthians. Timesitheus recovered the region before his death in 243. During the 250s, Persian shah Shapur I attacked Mesopotamia. He fought with Roman emperor Valerian whom he captured at Edessa in 260. Odaenathus of Palmyra took a stand against Shapur the next year. Shapur eventually retreated from the conflict.Diocletianic Administrative Reform