Early in 634, Caliph Abu Bakr issued summons for holy war and sent a force under the great Khalid to attack lower Iraq. He routed the Persian detachment and received the submission of the Arab Christians of Hira and fortress of Anbar. At this time Khalid was withdrawn from the Persian front and was ordered to proceed to Syria. General Muthanna remained on the front to deal with a vigorous Persian counter-offensive, led by the Sassanid General Rustom. Near the ruins of Babylon, he fell upon the Mujahideen. Persian elephants spread terror among Mujahideen cavalry and the ' Battle of Bridge ' (Nov. 634) ended in a disastrous setback to Muslims, injuring .Muthanna fatally and he died later

Sa'ad ibn Abi Wakkas, a seasoned warrior, who had fought at Badar and Uhud, was given the assignment of Persia by Caliph Omar. Rustom marched out of Ctesiphon and Mujahideen on the plain of Kadisiya, near Hira. The battle which was fought for four days in 637, was won by Mujahideen as Muslim lancers had discovered how to deal with the elephants by firing at their eyes and trunks. Rustom was killed. Beaten army retreated to Ctesiphon but the capital was ill fitted to stand a siege. The King and the court fled to Hulwan and Muslims occupied Ctesiphon, one of the finest cities in Asia, almost without resistance. Sa'ad pursued the enemy across the Tigris, beat Persians at Jalula and drove King Yazdegird from Hulwan also. Yazdegird who had retired to holy city Ray and there summoned the nation to a crusade against Muslims, Persians moved from Ray through Hamadan to Tigris. At Nihavand they encountered with Mujahideen, from the garrison of Basra and Kufa. Persians were completely routed. Later, Aizerbaijan was also conquered by Muslims.