The relationship between the Ottoman Empire and the Mamluks was adversarial: both states vied for control of the spice trade, and the Ottomans aspired to eventually take control of the Holy Cities of Islam. The two states however were separated by a buffer zone occupied by Turkmen states such as Karamanids, Aq Qoyunlu, Ramadanids, and Dulkadirids, which regularly switched their allegiance from one power to the other.

The Ottoman-Mamluk war took place from 1485 to 1491, when the Ottoman Empire invaded the Mamluk Sultanate territories of Anatolia and Syria. This war was an essential event in the Ottoman struggle for the domination of the Middle-East. After multiple encounters, the war ended in a stalemate and a peace treaty was signed in 1491, restoring the status quo ante bellum. It lasted until the Ottomans and the Mamluks again went to war in 1516–17.