He first appears in history as Philip's envoy to Athens, making peace in 347-346. He aided Alexander in the successional struggle after Philip's death, and during Alexander's campaign in the East, Antipater was governor of Macedonia and "general of Europe", posts he held from 334 to 323.
This was a busy post at first; tribes in Thrace rebelled in 332, followed shortly by the revolt of Agis III of Sparta, whom Antipater defeated near Megalopolis in 331. Antipater was disliked for supporting oligarchs and tyrants in Greece, but he also worked with the Greek League of Philip.
After the death of Alexander, Antipater faced revolts in Athens, Aetolia, and Thessaly that made up the Lamian War, but defeated them in the Battle of Crannon and broke up the rebellion. As part of this he imposed oligarchy upon Athens and demanded the surrender of Demosthenes, who committed suicide instead.
In 321, along with other generals, he opposed Perdiccas, and after Perdiccas' death, a conference of generals at Triparadisus in Syria chose him as regent. He died in 319 however, and with his death the breakup of the empire, sometimes known as Alexander's Funeral Games, began in earnest.