The conflict started when the Mamluk Sultan Baibars, seeking to take advantage of the weakened Mongol domination, sent a 30,000 strong army to Cilicia and demanded that Hethum I of Armenia abandon his allegiance to the Mongols, accept himself as a suzerain, and give to the Mamluks the territories and fortresses Hetoum has acquired through his alliance with the Mongols. At the time however, Hetoum I was in Tabriz, having gone to the Mongol court of the Il-Khan in Persia to obtain military support. During his absence, the Mamluks marched on Cilician Armenia, led by Al-Mansur Ali and the Mamluk commander Qalawun. Hetoum I's two sons, Leo (the future king Leo II) and Thoros, led the defense by strongly manning the fortresses at the entrance of the Cilician territory with a 15,000 strong army.

The confrontation took place at Mari, near Darbsakon on 24 August 1266, where the heavily outnumbered Armenians were unable to resist the much larger Mamluk forces. Thoros was killed in battle, and Leo was captured and imprisoned. The Armeno-Mongol son of the Constable Sempad, named Vasil Tatar, was also taken prisoner by the Mamluks and was taken into captivity with Leo, although they are reported to have been treated well. Het'um ransomed Leo for a high price, giving the Mamluks control of many fortresses and a large sum of money.

Following their victory, the Mamluks invaded Cilicia, ravaging the three great cities of the Cilician plain: Mamistra, Adana and Tarsus, as well as the harbour of Ayas. Another group of Mamluks under Mansur took the capital of Sis which was sacked and burnt, thousands of Armenians were massacred and 40,000 taken captive.