Cilician Armenia at the time was in a volatile situation, maintaining a fragile relationship as a vassal state of the Mongol Empire, while defending from attacks by the Muslim Mamluks from the south.

The throne of Armenia had changed hands multiple times during Leo's brief lifetime, being held variously by his uncle Hethum II in 1295, passed peacefully to his father Thoros III in 1296, then usurped by another uncle Sempad, who was usurped by his brother Constantine III of Armenia, who himself was deposed by his brother Hethum II in 1299.

In 1305, Hethum and Leo led the Armenian army to defeat a Mamluk raiding force at Bagras.

On November 17, 1307, Leo and Hethum were murdered with their retinue at a banquet while visiting the Mongol general Bilarghu at Anazarbus.

Bilarghu, a Mongol who had converted to Islam, had sought to build a mosque in the capital city of Sis, but Hethum had blocked the move as he wanted Armenia to be a completely Christian kingdom and complained to the leader of the Mongol Ilkhanate, Oljeitu.