Like the Achaemenid and Parthian kings before them, the Sasanian rulers were followers of the prophet Zoroaster (Zarathustra). With the conquests of the first king, Ardashir, who is sometimes depicted receiving power from Ahuramazda (the supreme god of the Zoroastrian pantheon), a formal state church was established.

However, trade with the Mediterranean, India and China encouraged the spread and blending of religious ideas and traditions. Christians enjoyed prominent roles, there was a large Jewish population in southern Mesopotamia as well as Buddhists and other religious faiths. After the death of Shapur I (reigned 241-272) there was a short-lived reversal of policy led by a Zoroastrian priest called Kartir. Manichaeans, Buddhists, Jews and Christians were persecuted. Strict adherence to the Zoroastrian faith was temporarily enforced.

By 300 more liberal policies were restored. Nonetheless, with Christianity increasingly becoming the religion of the Roman Empire (the emperor Constantine converted in 312) some Christians in Iran were persecuted under Shapur II (reigned 309-379) although the Persian Church maintained an archbishop at Ctesiphon, the Sasanian capital. With the Arab conquest of the Sasanian Empire in the 7th century, followed by the resettlement of large numbers of Muslims to some parts of the empire, Zoroastrianism became a minority religion in Iran.