Arrian tells us he was son of Orontes, a descendant of the independent princes of the province of Orestis. As the commander of a battalion of heavy phalanx infantry, Perdiccas distinguished himself during the conquest of Thebes (335 BC), where he was severely wounded. Subsequently he held an important command in the Indian campaigns of Alexander. When Hephaestion unexpectedly died in 324 BC, he was appointed his successor as commander of the Companion cavalry and chiliarch (vizier). Also in 324, at the nuptials celebrated at Susa, Perdiccas married the daughter of the satrap of Media, a Persian named Atropates.
In the Partition of Babylon made after Alexander's death (323 BC) Alexander's generals agreed that Philip III of Macedon, an epileptic illegitimate son of Alexander's father Philip II of Macedon, and the unborn child of Alexander's wife Roxana should be recognized as joint kings. Perdiccas was appointed guardian and regent of the empire. He soon showed himself intolerant of any rivals, and, acting in the name of the two kings (Roxana gave birth to a son, Alexander), sought to hold the empire together under his own hand. He had Meleager, the infantry commander, arrested and murdered.
Perdiccas' most loyal supporter was Eumenes, governor of Cappadocia and Paphlagonia. These provinces had not yet been conquered by the Macedonians. Antigonus (governor of Phrygia, Lycia and Pamphylia) refused to undertake the task when Perdiccas ordered him to. Having been summoned to the royal presence to stand his trial for disobedience, Antigonus fled to Europe and entered an alliance with Antipater, Craterus and Ptolemy against him.
Leaving the war in Asia Minor to Eumenes, Perdiccas marched to attack Ptolemy in Egypt. He reached Pelusium but failed to cross the Nile. A mutiny broke out amongst his troops, disheartened by failure and exasperated by his severity. Perdiccas was assassinated by his officers (Peithon, Antigenes, and Seleucus) sometime in either 321 or 320 BC. Problems with the chronology of Diodorus have led to uncertainty as to the year in which he died.