The Ottoman–Mamluk War of 1516–1517 was the second major conflict between the Egypt-based Mamluk Sultanate and the Ottoman Empire, which led to the fall of the Mamluk Sultanate and the incorporation of the Levant, Egypt, and the Hejaz as provinces of the Ottoman Empire. The war transformed 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 much of the traditional lands of Islam, including the cities of Mecca, Cairo, Damascus, and Aleppo. Despite this expansion, the seat of the empire's political power remained in Constantinople.

The Mamluk Sultanate, also known as Mamluk Egypt or the Mamluk Empire, was a state that ruled Egypt, the Levant and the Hejaz from the mid-13th to early 16th centuries. It was ruled by a military caste of mamluks headed by a sultan. The sultanate was established with the overthrow of the Ayyubid dynasty in Egypt in 1250 and was conquered by the Ottoman Empire in 1517. Mamluk history is generally divided into the Turkic or Bahri period (1250–1382) and the Circassian or Burji period (1382–1517), called after the predominant ethnicity or corps of the ruling Mamluks during these respective eras.