In 1260, Baibars, the Sultan of Egypt and Syria, began to threaten the Principality of Antioch, a Crusader state, which (as a vassal of the Armenians) had supported the Mongols. In 1265, Baibars took Caesarea, Haifa and Arsuf. A year later, Baibars conquered Galilee and devastated Cilician Armenia. The siege of Antioch occurred in 1268 when the Mamluk Sultanate under Baibars finally succeeded in capturing the city of Antioch.

The Hospitaller fortress Krak des Chevaliers fell three years later. While Louis IX of France launched the Eighth Crusade ostensibly to reverse these setbacks, it went to Tunis, instead of Constantinople, as Louis' brother, Charles of Anjou, had initially advised, though Charles I clearly benefited from the treaty between Antioch and Tunis that ultimately resulted from the Crusade.

By the time of his death in 1277, Baibars had confined the Crusaders to a few strongholds along the coast and they were forced out of the Middle East by the beginning of the fourteenth century. The fall of Antioch was to prove as detrimental to the crusaders cause as its capture was instrumental in the initial success of the first Crusade.