In ad 224 Ardashir I, a Persian vassal-king, rebelled against the Parthians, defeated them in the Battle of Hormuz, and founded a new Persian dynasty, that of the Sassanids. He then conquered several minor neighboring kingdoms, invaded India, levying heavy tribute from the rulers of the Punjab, and conquered Armenia. A particularly significant accomplishment of his reign was the establishment of Zoroastrianism as the official religion of Persia. Ardashir was succeeded in 241 by his son Shapur I, who waged two successive wars against the Roman Empire, conquering territories in Mesopotamia and Syria and a large area in Asia Minor. Between 260 and 263 he lost his conquests to Odenathus, ruler of Palmyra, and ally of Rome. War with Rome was renewed by Narses; his army was almost annihilated by Roman forces in 297, and he was compelled to conclude peace terms whereby the western boundary of Persia was moved from the Euphrates River to the Tigris River and much additional territory was lost. Shapur II (ruled 309-379) regained the lost territories, however, in three successive wars with the Romans.
The next ruler of note was Yazdegerd I, who reigned in peace from 399 to 420; he at first allowed the Persian Christians freedom of worship and may even have contemplated becoming a Christian himself, but he later returned to the Zoroastrianism of his forebears and launched a 4-year campaign of ruthless persecution against the Christians. The persecution was continued by his son and successor, Bahram V, who declared war on Rome in 420. The Romans defeated Bahram in 422; by the terms of the peace treaty the Romans promised toleration for the Zoroastrians within their realm in return for similar treatment of Christians in Persia. Two years later, at the Council of Dad-Ishu, the Eastern church declared its independence of the Western church.
Near the end of the 5th century a new enemy, the barbaric Ephthalites, or “White Huns,” attacked Persia; they defeated the Persian king Firuz II in 483 and for some years thereafter exacted heavy tribute. In the same year Nestorianism was made the official faith of the Persian Christians. Kavadh I favored the communistic teachings of Mazdak (flourished 5th century), a Zoroastrian high priest, and in 498 was deposed by his orthodox brother Zamasp. With the aid of the Ephthalites, Kavadh was restored to the throne in 501. He fought two inconclusive wars against Rome, and in 523 he withdrew his support of Mazdak and caused a great massacre of Mazdak’s followers. His son and successor, Khosrau I, in two wars with the Byzantine emperor Justinian I, extended his sway to the Black Sea and the Caucasus, becoming the most powerful of all Sassanid kings. He reformed the administration of the empire and restored Zoroastrianism as the state religion. His grandson Khosrau II reigned from 590 to 628. In 602, despite having won the throne with the help of the Byzantine emperor Maurice, he began a long war against the Byzantine Empire. By 619 he had conquered almost all southwestern Asia Minor and Egypt. Further expansion was prevented by the Byzantine emperor Heraclius, who between 622 and 627 drove the Persians back within their original borders. The last of the Sassanid kings was Yazdegerd III, during whose reign (632-651) Arab Muslims invaded and eventually conquered Persia. For the post-Sassanid history of the region.