Before marching towards Antioch, Khalid and Abu Ubaidah decided to isolate the city from Anatolia. They accordingly sent detachments north to eliminate all possible Byzantine forces and captured the garrison town of Azaz, 50 kilometres from Aleppo; from there Muslims attacked Antioch from the eastern side, resulting in the Battle of Iron bridge.

The Byzantine army, composed of the survivors of Yarmouk and other Syrian campaigns, was defeated, retreating to Antioch, whereupon the Muslims besieged the city. Having little hope of help from the Emperor, Antioch surrendered on 30 October, on the condition that all Byzantine troops would be given safe passage to Constantinople.