In the 1250s Qalāʾūn was an early and devoted supporter of the Mamlūk commander Baybars (Baybars I), and, after the latter became sultan of Egypt and Syria in 1260, Qalāʾūn's career advanced rapidly. Upon the death of Baybars in 1277, Qalāʾūn quickly deposed and exiled two of Baybars' sons who had briefly succeeded to the sultanate, and in 1279 Qalāʾūn himself became sultan of Egypt. He solidified his power after fighting off a rival claimant to the throne in 1280, and he thereupon proceeded to consolidate the Mamlūk position in the Middle East.

Qalāʾūn wished both to expel the Latin (Christian) crusaders from their remaining footholds in the Middle East and to repel the invading Mongols. He made a truce with the Knights Templars and then ended the Mongol threat to Egypt by defeating the Mongols at the Battle of Homs in 1281. In 1289 he broke his truce with the crusaders and captured the fortified port of Tripoli, which was then the largest town still held by the crusaders. Qalāʾūn died while mounting a campaign to besiege the town of Acre. He was succeeded as sultan by his son Khalīl, who successfully wrested Acre from the crusaders in 1291. Qalāʾūn was a decisive ruler and an able administrator. He encouraged trade and public-welfare activities in Egypt and was responsible for building the Qalāʾūn Mosque complex.