Ardashir I had, towards the end of his reign, renewed the war against the Roman Empire, and Shapur I had conquered the Mesopotamian fortresses Nisibis and Carrhae and had advanced into Syria. In 242, the Romans under the father-in-law of their child-emperor Gordian III set out against the Sasanians with "a huge army and great quantity of gold," (according to a Sasanian rock relief) and wintered in Antioch, while Shapur was occupied with subduing Gilan, Khorasan, and Sistan.

The Romans later invaded eastern Mesopotamia but faced tough resistance from Shapur I who returned from the East. The young emperor Gordian III went to the Battle of Misiche and was either killed in the battle or murdered by the Romans after the defeat. The Romans then chose Philip the Arab as Emperor. Philip was not willing to repeat the mistakes of previous claimants, and was aware that he had to return to Rome to secure his position with the Senate. Philip concluded a peace with Shapur I in 244; he had agreed that Armenia lay within Persia's sphere of influence. He also had to pay an enormous indemnity to the Persians of 500,000 gold denarii.