In 338 BC, the Persian king Artaxerxes III died. He was succeeded by Artaxerxes IV (better known as Arses), who was murdered by Darius III -a very successful general and a member of the royal family- in 336. An eunuch named Bogoas served as king maker, but the new king had him executed. This was a bad moment for civil strive, because in faraway Macedonia, king Philippus was preparing a full scale attack on the Persian empire, as a revenge for Xerxes' expedition to Europe. The Macedonian king was assassinated (Persian interference was suspected, but is unlikely), but he was succeeded by his crown prince, Alexander, who executed his father's plans: in May 334, Darius' satraps were defeated at the river Granicus in the northwest of modern Turkey. It was a very bad start of a reign.

Worse was to come. During the battles at Issus and Gaugamela (November 333 and October 1, 331), in which Darius took part, he was unable to defend his kingdom against the Macedonians. In the first weeks of 330, Alexander reached the Persian heartland and set Persepolis afire. This was too much fort the Persian nobility, and the king was killed by Bessus.

Alexander gave Darius a royal burial and pursued his murders, who were executed on a charge of regicide.