With his brother Podalirius, he led an army from Thessaly in the Trojan War on the side of the Greeks. Both Machaon and Podalirius were highly valued surgeons and medics. He was wounded and put out of action by Paris. Machaon (or his brother) healed Philoctetes, Telephus and Menelaus, after he sustained an arrow at the hand of Pandarus, during the war. He was also supposed to possess herbs which were bestowed to his father Asclepius by Chiron, the centaur.
He was killed by Eurypylus in the tenth year of the war. He was buried in Gerenia in Messenia, where he was worshiped by the people.