An established religion did not make a uniform empire. Mani, born in Mesopotamia around 216, preached a teaching that drew on Zoroastrian, Christian and Buddhist material and was for a time favoured at court under Shapur I; under Bahram I he was arrested and died in prison in the 270s, and his followers were driven east and west, carrying Manichaeism as far as China.
Christianity in Persia was at first suspect precisely because Rome had adopted it, and the fourth century brought severe persecutions under Shapur II. The resolution was structural: at the synod of Seleucia-Ctesiphon in 410 the Persian church was organised under its own catholicos with imperial recognition, and by taking a theological line distinct from Constantinople it became demonstrably not a Roman fifth column. That Church of the East then sent missions along the Silk Road as far as Tang China.
The Jewish communities of Babylonia lived under their own exilarch through the same centuries, and the academies of Sura and Pumbedita produced, under Sasanian rule, the Babylonian Talmud, the most consequential document of rabbinic Judaism.
The empire ended quickly. Exhausted by a generation of war with Byzantium, it lost at Qadisiyya and Nahavand in the 630s and 640s, and the last king was killed in 651. Zoroastrianism persisted for centuries as a diminishing minority, and a community that migrated to Gujarat became the Parsis.