Suleiman's father had made war with Persia a high priority. At first, Suleiman shifted attention to Europe and was content to contain Persia, which was preoccupied by its own enemies to its east. After Suleiman stabilized his European frontiers, he now turned his attention to Persia, the base for the rival Islamic faction of Shi'a. The Safavid dynasty became the main enemy after two episodes.

The war was triggered by territorial disputes between the two empires, especially when the Bey of Bitlis decided to put himself under Persian protection. Also, Tahmasp had the governor of Baghdad, a sympathiser of Suleiman, assassinated. On the diplomatic front, Safavids had been engaged in discussions with the Habsburgs for the formation of a Habsburg–Persian alliance that would attack the Ottoman Empire on two fronts.