Peithon was the son of Crateuas, a nobleman from Eordia in western Macedonia. He took part in the campaign of Alexander the Great, and is first mentioned as a trierarch in 326. Trierarchs were the builders and nominal commanders of ships; in this case, the most influential courtiers of Alexander helped him build ships to navigate the river Indus. Next year, he was appointed as one of Alexander's seven bodyguards.
There is a strange report that when Alexander was on his death bed, Peithon, Seleucus, Peucestas, and several others visited the temple of Serapis in Babylon, spent the night, and asked the god what to do. He answered that the king should remain where he was; soon after Alexander heard the news, he died (11 June 323). The problem is that Serapis was a Greek adaptation of an Egyptian god from the early thrid century, a generation after the death of Alexander. It is impossible to establish the historical value of the anecdote.
After his death, Perdiccas was made regent because Alexander's half-brother Philip Arridaeus was mentally unfit to rule. At Babylon, the satrapies were divided, and Peithon was made satrap of Media, the strategically important region that controlled all roads between east and west (e.g., the Silk road). Actually, the satrapy was too large for one man: Peithon would be a very powerful man, and could destabilize the entire empire. Therefore, he had to give up the northern part, which was given to Atropates.
Peithon was immediately involved in a full-scale war, because the veterans who had been forced by Alexander to live in punitive colonies in the eastern satrapies, decided to fight themselves a way back to Greece (text). Peithon defeated them and sent them back home, showing that he was a very capable general. Contrary to Perdiccas' orders, however, he accepted the capitulation of his opponents and offered very reasonable terms. This was intelligent, because Macedonian manpower in the east was low, and the eastern satraps could not afford to lose their men. Unfortunately, Peithon's soldiers disobeyed: led on by hopes of plunder, they massacred many veterans. This was the worst of all possible outcomes: not only was there a considerable loss of manpower, but Perdiccas had started to distrust Peithon as well.
However, he was not strong enough to replace the satrap of Media, and therefore demanded his help at all possible occasions. Peithon probably had to join Perdiccas' campaign against Ariarathes, a native leader in Cappadocia. In this way, the regent could control him.
Perdiccas' regency started with a success that augured well for the future unity of the empire: the veterans, the Cappadocians and the insurgent Greeks were all defeated within one year. However, he made one big mistake: when Alexander's full sister Cleopatra offered him her hand, he accepted the marriage, and offended the supreme commander of the Macedonian forces in Europe, Antipater, because he was already engaged to his daughter Nicaea.
This was the immediate cause of the First War of the Diadochi, the successors of Alexander. However, offended pride was not the real cause. What made war inevitable was the growth of Perdiccas' power and the fear which this caused among the other Macedonian leaders - Antipater in the first place, but also Craterus, Antigonus Monophthalmus, and the satrap of Egypt, Ptolemy.
Perdiccas decided to invade Egypt, and ordered Peithon to join the expedition. Twice, the expeditionary force tried to cross the Nile near Pelusium, but Ptolemy was able to prevent this. Now, Perdiccas moved to the apex of the Delta, and retried the river crossing in the neighborhood of Heliopolis. However, his men were carried away by the Nile. To all those present, it was obvious that Perdiccas could never invade Egypt, and his soldiers revolted. Perdiccas sought the advice of Peithon, Antigenes, and Seleucus. They, however, decided to kill their general, to put an end to the civil war (summer 320).
Ptolemy started negotiations with Perdiccas' officers. They offered the Egyptian ruler the regency, but he was too intelligent to accept this offer: he was not a gambler and wanted to keep what he had, not risking it in a larger game. Therefore, he appointed Peithon and an officer named Arridaeus. The latter's only merit was that he had been the first officer of Perdiccas to change sides, and he was detested by the defeated army. Peithon certainly had more prestige, but it was easy to see that the new regents lacked personal influence and would never be able to stop separatists like Ptolemy.
This outcome was considered outrageous and therefore, a conference was organized at Triparadisus (in the valley of the Orontes in Syria), in 320. Antipater, the commander of the Macedonian forces in Europe, was chosen as the new regent; Antigonus Monophthalmus became the supreme commander of the Macedonian forces in Asia; Peithon and Arridaeus were forced to accept demotion; the satrapies were divided again. This was the result of the conference at Triparadisus (320).
Understandably, Peithon felt cheated, and when he heard that Antipater had died, he decided to use his forces to enlarge his power. His victim was Philip, the satrap of Parthia (318). He overcame his resistance and made his brother Eudamus satrap. However, the other satraps in the east united to drive the two men back. They defeated Peithon once, he had to give up Parthia, and they were ready for the final attack when Peithon was miraculously saved.
After the death of Antipater, an officer named Polyperchon had been made regent, but he had to fight for the regency with Antipater's son Cassander. In this confused situation, Antigonus had attempted to enlarge his power in Asia, and he had launched a war against Eumenes, who had been recognized as commander of the Macedonian forces in Asia by Polyperchon. Antigonus pursued Eumenes, who went to Babylonia and Susa. Here, he met the army of the eastern satraps, which decided to join forces with Eumenes. In this way, Peithon survived. In January 315, Antigonus defeated his opponent, and returned to the west, leaving Peithon as the strongest ruler in the eastern half of the empire.
Immediately, Peithon started to rebuild his power base. Antigonus, however, was not a man of half measures. He lured the satrap if Media to his court, arrested him, accused him, and had Peithon executed.