His reign was largely uneventful; to the west, a dispute with the Romans over Armenia was eventually settled through diplomacy, partitioning the area between the two empires in a manner which left most of it under Sasanian control.

To the east, Shapur III lost control of the important mint city Kabul to the Alchon Huns.

He was the penultimate monarch to have a rock relief carved, the last one being Khosrow II (r. 590–628), who mimicked and magnified Shapur III's work.

Derived from Old Iranian *xšayaθiya.puθra ("son of a king"), it must initially have been a title, which became—at least in the late 2nd century AD—a personal name.

The reason behind this was due to his continuation of Shapur II's policy of restricting the authority of power-hungry nobles.

Shapur III responded by crowning Khosrov IV as king, and gave him his sister Zurvandukht in marriage.

[12][6] The boundary stretched through Theodosiopolis in the north and Amida in the south, which meant that most of Armenia remained in Sasanian hands,[6] including the two Arsacid capitals of Artaxata and Dvin.

[6] Both sides were to cooperate in the defense of the Caucasus, with the Romans agreeing to pay the Iranians roughly 500 lbs (226 kg) of gold at irregular intervals.

[13][20][24] Arshak III soon died, which made the Romans abolish their branch of the Arsacid monarchy and create the province of Western Armenia.

[7][6] Shapur III's religious tolerance towards the Christians is reported by the historians Elishe and John of Ephesus.

According to the former, Shapur III granted the Armenians lavish gifts and exempted their Church from royal taxation.

[28] Under Shapur III and Bahram IV, the administrative program for Sasanian coinage substantially changed.

[31][32] Shapur III ordered the creation of a rock relief located at the site of Taq-e Bostan near present-day Kermanshah.

[33] Unlike other Sasanian reliefs, the one created under Shapur III was not sculptured at the surface of a rock face, but at the back of a barrel vaulted area.