In 295 or 296, Narseh declared war on Rome. He appears to have first invaded western Armenia, retaking the lands delivered to King Tiridates III of Armenia in the peace of 287. Narseh then moved south into Roman Mesopotamia, where he inflicted a severe defeat on Galerius, then commander of the Eastern forces, in the region between Carrhae (Harran, Turkey) and Callinicum (Raqqa, Syria). However in 298, Galerius defeated the Persians in the Battle of Satala in 298, sacking the capital Ctesiphon, capturing the treasury and the royal harem.

The battle was followed by the Treaty of Nisibis, highly advantageous to Rome. It ended the Roman–Sasanian war; Tiridates was restored to his throne in Armenia as a Roman vassal, and the Georgian Kingdom of Iberia was acknowledged as also falling under Roman authority. Rome itself received a part of Upper Mesopotamia that extended even beyond the Tigris - including the cities of Tigranokert, Saird, Martyropolis, Balalesa, Moxos, Daudia, and Arzan.