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 Shia Muslim faction. The Safavid dynasty became the main enemy after two episodes. First, Shah Tahmasp killed the Baghdad governor loyal to Suleiman, and put his own man in. Second, the governor of Bitlis had defected and sworn allegiance to the Safavids.^[19]: 51 As a result, in 1533, Suleiman ordered his Pargalı Ibrahim Pasha to lead an army into eastern Asia Minor where he retook Bitlis and occupied Tabriz without resistance. Suleiman joined Ibrahim in 1534. They made a push towards Persia, only to find the Shah sacrificing territory instead of facing a pitched battle, resorting to harassment of the Ottoman army as it proceeded along the harsh interior.^[33] In 1535 Suleiman made a grand entrance into Baghdad. He enhanced his local support by restoring the tomb of Abu Hanifa, the founder of the Hanafi school of Islamic law to which the Ottomans adhered.^[34]

Attempting to defeat the Shah once and for all, Suleiman embarked upon a second campaign in 1548–1549. As in the previous attempt, Tahmasp avoided confrontation with the Ottoman army and instead chose to retreat, using scorched earth tactics in the process and exposing the Ottoman army to the harsh winter of the Caucasus.^[33] Suleiman abandoned the campaign with temporary Ottoman gains in Tabriz and the Urmia region, a lasting presence in the province of Van, control of the western half of Azerbaijan and some forts in Georgia.^[35]

In 1553, Suleiman began his third and final campaign against the Shah. Having initially lost territories in Erzurum to the Shah’s son, Suleiman retaliated by recapturing Erzurum, crossing the Upper Euphrates and laying waste to parts of Persia. The Shah’s army continued its strategy of avoiding the Ottomans, leading to a stalemate from which neither army made any significant gain. In 1555, a settlement known as the Peace of Amasya was signed, which defined the borders of the two empires. By this treaty, Armenia and Georgia were divided equally between the two, with Western Armenia, western Kurdistan, and western Georgia (incl. western Samtskhe) falling in Ottoman hands while Eastern Armenia, eastern Kurdistan, and eastern Georgia (incl. eastern Samtskhe) stayed in Safavid hands.^[36] The Ottoman Empire obtained most of Iraq, including Baghdad, which gave them access to the Persian Gulf, while the Persians retained their former capital Tabriz and all their other northwestern territories in the Caucasus and as they were prior to the wars, such as Dagestan and all of what is now Azerbaijan.^[37][38