Umar ordered his army to retreat to the Arabian border and began raising armies at Medina for another campaign into Mesopotamia. Umar appointed Saad ibn Abi Waqqas, a respected senior officer. Saad left Medina with his army in May 636 and arrived at Qadisiyyah in June.

While Heraclius launched his offensive in May 636, Yazdegerd was unable to muster his armies in time to provide the Byzantines with Persian support. Umar, allegedly aware of this alliance, capitalized on this failure: not wanting to risk a battle with two great powers simultaneously, he quickly moved to reinforce the Muslim army at Yarmouk to engage and defeat the Byzantines. Meanwhile, Umar ordered Saad to enter into peace negotiations with Yazdegerd III and invite him to convert to Islam to prevent Persian forces from taking the field. Heraclius instructed his general Vahan not to engage in battle with the Muslims before receiving explicit orders; however, fearing more Arab reinforcements, Vahan attacked the Muslim army in the Battle of Yarmouk in August 636, and was routed.

With the Byzantine threat ended, the Sassanid Empire was still a formidable power with vast manpower reserves, and the Arabs soon found themselves confronting a huge Persian army with troops drawn from every corner of the empire, including war elephants, and commanded by its foremost generals. Within three months, Saad defeated the Persian army in the Battle of al-Qādisiyyah, effectively ending Sassanid rule west of Persia proper. This victory is largely regarded as a decisive turning point in Islam's growth: