Oxyathres was a son of Arsanes and Sisygambis, members of a minor branch of the Achaemenid dynasty that ruled the Persian empire. Because Oxyathres was younger than his brother Artašata (the future king Darius III), who was born in c.380, we may assume that he was born in c.380-375.
According to our sources, Oxyathres fought to protect his brother during his battle against Alexander the Great near Issus (November 333). The story is told by Diodorus of Sicily:
The Persian Oxyathres was the brother of Darius and a man highly praised for his fighting qualities. When he saw Alexander riding at Darius and feared that he would not be checked, he was seized by the desire to share his brother's fate. Ordering the best of the horsemen in his company to follow him, he threw himself with them against Alexander, thinking that this demonstration of brotherly love would bring him high renown among the Persians. He took up the fight directly in front of Darius' chariot and there, engaging the enemy skillfully and with a stout heart slew many of them. The fighting qualities of Alexander's group were superior, however, and quickly many bodies lay piled high about the chariot. No Macedonian had any other thought than to strike the king, and in their intense rivalry to reach him took no thought for their own lives. Many of the noblest Persian princes perished in this struggle.note[Diodorus, World History, 17.34.1-5; tr. C. Bradford Welles.]
Oxyathres' heroic behavior is shown on the Alexander mosaic (although there are other interpretations). From the left, we see Alexander -without helmet!- approaching and aiming a lance at Darius in the chariot. Oxyathres is right in front of Alexander, standing over his dead horse. He has seized the lance, which has gone through his garments, and pushes it away. To the right, Darius' charioteer is trying to make a turn. From Diodorus, we know that the horses were scared of the dead bodies, which forced the great king to leave his chariot.
Oxyathres survived the battle and accompanied his brother to the east, and stayed with him to the very end. After a distant relative named Bessus had murdered Darius in July 330, Oxyathres sided with Alexander, who had announced that he wanted to avenge the assassination. Oxyathres remained at the Macedonian court, belonged to the king's Companions, and may have been the first among Alexander's Persian bodyguards.
Pursuing Bessus, the Macedonians crossed the Hindu Kush, the Bactrian desert and the river Oxus. Bessus' courtiers Spitamenes and Datames were freightened, arrested Bessus and handed him over to the Macedonians. The king had Bessus cruelly mutilated: his ears and nose were cut off. This was shocking to the Europeans, but it was what Alexander had to do as a Persian king who punished a regicide. Two centuries before, Darius the Great had ordered the same treatment for Phraortes, the last ruler of independent Media (see Behistun inscription, section 32).
After the mutilation, Alexander handed Bessus over to Oxyathres, ordering that he should bring the assassin to the place where he had killed his master, crucify him and keep the vultures away from the dead body. This was a very gruesome deed: the Zoroastrians believed that the dead must be devoured by birds. It was the Persian equivalent of the Greek denial of burial.
Oxyathres had a daughter named Amastris, who was born c.350. During the weddings at Susa (early 324), she was married to Alexander's general Craterus.