He came to the throne after the ten years of confusion which followed the death of Archelaus II, the patron of art and literature. But he had many enemies at home; in 393 he was driven out by the Illyrians, but in the following year, with the aid of the Thessalians, he recovered his kingdom. Medius, head of the house of the Aleuadae of Larissa, is believed to have provided aid to Amyntas in recovering his throne. The mutual relations between the Argeadae and the Aleuadae dates to the time of Archelaus.
To shore up his country against the threat of the Illyrians, Amyntas established an alliance with the Chalcidic cities led by Olynthus. In exchange for this support, Amyntas granted them rights to Macedonian timber, which was sent back to Athens to help fortify their fleet. With money flowing into the Olynthus from these exports, their power grew. In response, Amyntas sought additional allies. He established connections with Kotys, chief of the Odrysians. Kotys had already married his daughter to the Athenian general Iphicrates. Prevented from marrying into Kotys' family, Amyntas soon adopted Iphicrates as his son.
After the King's Peace 387 BC, Sparta was anxious to reestablish its presence in the north of Greece. In 385 BC, Bardylis and his Illyrians attacked Epirus instigated and aided by Dionysius of Syracuse , in an attempt to restore the Molossian king Alcetas to the throne. When Amyntas sought Spartan aid against the growing threat of Olynthus, the Spartans eagerly responded. That Olynthus was backed by Athens and Thebes, rivals to Sparta for the control of Greece, provided them additional incentive to break up this growing power in the north. Amyntas thus concluded a treaty with the Spartans, who assisted him to reduce Olynthus (379). He also entered into a league with Jason of Pherae, and assiduously cultivated the friendship of Athens.In 371 BC at a Panhellenic congress of the Lacedaemonian allies, he voted in support of the Athenians' claim and joined other Greeks in voting to help Athens to recover possession of Amphipolis.
With Olynthus defeated, Amyntas was now able to conclude a treaty with Athens and keep the timber revenues for himself. Amyntas shipped the timber to the house of the Athenian Timotheus, in the Piraeus.
By his wife, Eurydice, he had three sons, Alexander II, Perdiccas III and the youngest of whom was the famous Philip II of Macedon. Amyntas died at an advanced age, leaving his throne to his eldest son, Alexander.