The Euphrates-Tigris Expedition was a military expedition conducted by the Ottoman Army against the Safavids and the Mamluks. It resulted in a victory for the Ottoman Empire.

Background In 1514, Selim I attacked the Safavid Empire to stop the spread of Shiism into Ottoman dominions. Selim and Ismā'il had exchanged a series of belligerent letters prior to the attack. On his march to face Ismā'il, Selim had 50,000 Alevis massacred, seeing them as enemies of the Ottoman Empire.

Selim I defeated Ismā'il at the Battle of Chaldiran in 1514.Michael Axworthy Iran: Empire of the Mind (Penguin, 2008) p. 133 Ismā'il's army was more mobile and his soldiers better prepared, but the Ottomans prevailed due in large part to their efficient modern army, possession of artillery, black powder and muskets. Ismā'il was wounded and almost captured in battle, and Selim I entered the Iranian capital of Tabriz in triumph on 5 September, but did not linger. The Battle of Chaldiran was of historical significance: the reluctance of Shah Ismail to accept the advantages of modern firearms and the importance of artillery proved decisive. After the battle, Selim, referring to Ismail, stated that his adversary was: "Always drunk to the point of losing his mind and totally neglectful of the affairs of the state".

Expedition

Following their victory, the Ottomans captured the Safavid capital city of Tabriz on 7 September, which they first pillaged and then evacuated. That week's Friday sermon in mosques throughout the city was delivered in Selim's name. Selim was however unable to press on after Tabriz due to the discontent amongst the janissaries. The Ottoman Empire successfully annexed Eastern Anatolia (encompassing Western Armenia) and Upper Mesopotamia from the Safavids. These areas changed hands several times over the following decades; however, the Ottoman hold would not be set until the 1555 Peace of Amasya following the Ottoman–Safavid War (1532–1555). Effective governmental rule and eyalets would not be established over these regions until the 1639 Treaty of Zuhab.

Selim I launched an attack on the Mamluks in 1516. The Ottoman army and the Mamluk army met near Marj Dabiq. The Mamluk army advanced and on 20 August made camp at the plain of Marj Dabiq, a day's journey north of Aleppo. There, al-Ghawri and his men awaited the enemy's approach on this plain, where the sultanate's fate would soon be decided.

According to the History of Egypt composed by Muḥammad ibn Aḥmad ibn Iyas, the Mamluks arranged themselves with the Sultan occupying the center column. Sibay, the Governor of Damascus, commanded the right flank, and Khai'r Bey, governor of Aleppo, took the left.

The marshal Sûdûn Adjami was the first to enter combat, followed by Sibay, leading an experienced corps of veteran Mamluk warriors. They rushed into battle and managed to kill several thousand Ottoman soldiers in the first hours of fighting. This advantage forced the opposite Ottoman wing to begin a withdrawal, and the Mamluk forces under Sibay succeeded in taking several pieces of artillery and capturing some fusiliers. Selim considered retreat or requesting a truce.

It was at this point that the battle turned against the Mamluks. A rumor began to spread that al-Ghawri had ordered the recruits to hold their position, avoid combat, and leave the fighting to the veteran soldiers who were already engaged in battle. When Marshall Sûdûn Adjami and Sibay, who were leading the attack, were suddenly killed, panic broke out in the Mamluks' advancing right flank. Meanwhile, Khai'r Bey, in command of the left flank, called for a retreat. The fact that his forces were the first to quit the field was considered evidence of the man's betrayal.

Ibn Iyas offered the following account of the Mamluk defeat:

Selim I, welcomed by the inhabitants as a deliverer from the excesses of the Mamluks, entered Aleppo in triumph. He received the Abbasid caliph warmly, but upbraided the Islamic judges and jurists for their failure to check Mamluk misrule. Joined by Khai'r Bey and other Egyptian officers, he proceeded to the Citadel.

From Aleppo, he marched with his forces to Damascus, where terror prevailed. Beyond some attempts to protect the city by flooding the plain around, the remnants of the Mamluk forces had done nothing substantial to oppose the enemy. Discord amongst the emirs had paralyzed the army and prevented any decisive action that might have affected the subsequent course of events. Some of al-Ghawri's lieutenants supported Emir Janberdi Al-Ghazali as the new sultan, but others favoured the deceased ruler's son. As the Ottomans approached, however, resistance dissolved, as the remaining forces either went over to their side or fled to Egypt. Selim I entered Damascus in mid-October, and the inhabitants readily surrendered to the conquerors.

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