Alexios III had fled Constantinople on the approach of the Crusaders in 1203, but had not given up on his rights to the throne, and was determined to reclaim it. Kaykhusraw, having found in supporting Alexios's cause a perfect pretext for attacking Nicaean territory, sent an emissary to Theodore at Nicaea, calling upon him to relinquish his domains to the legitimate emperor. Theodore refused to reply to the sultan's demands, and the sultan assembled his army and invaded Laskaris' domains.

At the Battle of Antioch on the Meander, the Seljuk sultan sought out Laskaris, who was hard pressed by the attacking Turkish troops. Kaykhusraw charged his enemy and gave him a heavy blow on the head with a mace, so that the Nicaean emperor, dizzied, fell from his horse. Kaykhusraw was already giving orders to his retinue to carry Laskaris away, when the latter regained his composure and brought Kaykhusraw down by hacking at his mount's rear legs. The sultan too fell on the ground and was beheaded. His head was impaled on a lance and hoisted aloft for his army to see, causing the Turks to panic and retreat.

In this way Laskaris snatched victory from the jaws of defeat, although his own army was well-nigh destroyed in the process. The battle ended the Seljuk threat: Kaykhusraw's son and successor, Kaykaus I, concluded a truce with Nicaea on 14 June 1211, and the border between the two states would remain virtually unchallenged until the 1260s. The former emperor Alexios III, Laskaris's father-in-law, was also captured during the battle. Laskaris treated him well but stripped him of his imperial insignia and consigned him to the monastery of Hyakinthos in Nicaea, where he ended his days.