Shapur accompanied his father's campaigns against the Parthians, who - at the time - still controlled much of the Iranian plateau through a system of vassal states that the Persian kingdom had itself previously been a part of. Before an assembly of magnates, Ardeshir "judged him the gentlest, wisest, bravest and ablest of all his children" and nominated him as his successor. Shapur also appears as heir apparent in Ardeshir's investiture inscriptions at Naqsh-e Rajab and Firuzabad. The Cologne Mani-Codex indicates that, by 240, Ardeshir and Shapur were already reigning together. In a letter from Gordian III to his senate, dated to 242, the "Persian Kings" are referred to in the plural. Synarchy is also evident in the coins of this period that portray Ardashir facing his youthful son, and which are accompanied by a legend that indicates that Shapur was already referred to as king.
The date of Shapur's coronation remains debated, but 241 is frequently noted. That same year also marks the death of Ardeshir, and earlier in the year, his and Shapur's seizure and subsequent destruction of Hatra, about 100 km southwest of Nineveh and Mosul in present-day Iraq. According to legend, al-Nadirah, the daughter of the king of Hatra, betrayed her city to the Sassanids, who then killed the king and had the city razed. (Legends also have Shapur either marrying al-Nadirah, or having her killed, or both).
Ardashir I had, towards the end of his reign, renewed the war against the Roman Empire. Shapur I conquered the Mesopotamian fortresses Nisibis and Carrhae and advanced into Syria. Timesitheus, father-in-law of the young emperor, Gordian III, drove him back and defeated him at the Battle of Resaena in 243, regaining Nisibis and Carrhae. Timesitheus died shortly afterward, and Philip the Arab (244–249) murdered Gordian III after his defeat at the Battle of Misiche. Philip then concluded an ignominious peace with the Persians in 244. With the Roman Empire debilitated by Germanic invasions and the continuous elevation of new emperors after the death of Trajan Decius (251), Shapur I resumed his attacks.
Shapur conquered Armenia, invaded Syria, and plundered Antioch. Eventually, the Emperor Valerian (253–260) marched against him, but having been besieged in Edessa after a defeat nearby, he was seized when he attempted to meet for negotiations in 260. Shapur advanced into Asia Minor, but was driven back by defeats at the hands of Balista, who captured the royal harem. Septimius Odenathus, prince of Palmyra, rose in his rear, defeated the Persian army and regained all the territories Shapur had occupied. Shapur was unable to resume the offensive and lost Armenia again.
One of the great achievements of Shapur's reign was the defeat of the Roman Emperor Valerian. This is presented in a mural at Naqsh-e Rustam, where Shapur is represented on horseback wearing royal armour and crown. Before him kneels Philip the Arab, in Roman dress, asking for grace. In his right hand the king grasps the uplifted arms of what may be Valerian; one of his hands is hidden in his sleeve as the sign of submission. The same scene is repeated in other rock-face inscriptions. Shapur is said to have publicly shamed Valerian by using the Roman Emperor as a footstool when mounting his horse. Other sources contradict and note that in other stone carvings, Valerian is respected and never on his knees. This is supported by reports that Valerian and some of his army lived in relatively good conditions in the city of Bishapur and that Shapur enrolled the assistance of Roman engineers in his engineering and development plans.
Under Shapur's reign, the prophet Mani, the founder of Manichaeism, began his preaching in Western Iran, and the King himself seems to have favoured his ideas. The Shapurgan, Mani's only treatise in the Middle Persian language, is dedicated to Shapur.
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