The Ottoman–Mamluk War of 1516–1517 is the second major conflict between the Egypt-based Mamluk Sultanate and the Ottoman Empire, which leads to the fall of the Mamluk Sultanate and the incorporation of the Levant, Egypt and the Arabian Peninsula as provinces of the Ottoman Empire The war transforms the Ottoman Empire from a realm at the margins of the Islamic world, mainly located in Anatolia and the Balkans, to a huge empire encompassing the traditional lands of Islam, including the cities of Mecca, Cairo, Damascus and Aleppo.

It continues to be ruled, however, from Constantinople.