Antigonus was appointed governor of Greater Phrygia in 333 BC, and in the division of the provinces after Alexander's death in 323 BC he also received Pamphylia and Lycia from Perdiccas, regent of the empire. He incurred the enmity of Perdiccas, the regent, by refusing to assist Eumenes to obtain possession of the provinces allotted to him. In danger of his life he escaped with his son Demetrius into Greece, where he obtained the favour of Antipater, regent of Macedonia (321 BC). Soon after, on Perdiccas's death in 321 BC, a new division of empire took place. Antigonus found himself entrusted with the command of the war against Eumenes, who had joined Perdiccas against the coalition of Antipater, Antigonus, Ptolemy, Craterus, and the other generals. Eumenes was defeated and forced to retire to the fortress of Nora in Cappadocia, and a new army that was marching to his relief was routed by Antigonus.
Polyperchon succeeded Antipater regent of the empire in 319 BC, to the exclusion of Cassander, his son. Antigonus resolved to set himself up as lord of all Asia, and in conjunction with Cassander and Ptolemy of Egypt, refused to recognize Polyperchon. He entered into negotiations with Eumenes; but Eumenes remained faithful to the royal house. Effecting his escape from Nora, he raised an army, and formed a coalition with the satraps of the eastern provinces. Antigonus fought against Eumenes two great battles at Paraitacene in 317 BC and Gabiene in 316 BC, following which Eumenes was at last delivered up to Antigonus through treachery in Persia and put to death (316 BC).
Antigonus again claimed authority over most Asia, seized the treasures at Susa and entered Babylon, of which Seleucus was governor. Seleucus fled to Ptolemy and entered into a league with him, Lysimachus and Cassander (315 BC) against Antigonus. In 314 BC Antigonus invaded Syria, under Ptolemy's control, and besieged Tyre for more than a year. His son Demetrius was defeated at the Battle of Gaza by Ptolemy in 312 BC, and during the Babylonian War, Seleucus defeated both Demetrius and Antigonus, and conquered Babylonia.
After the war had been carried on with varying success from 315 to 311, peace was concluded, by which the government of Asia Minor and Syria was provisionally secured to Antigonus. This agreement was soon violated on the pretext that garrisons had been placed in some of the free Greek cities by Antigonus, and Ptolemy and Cassander renewed hostilities against him. Demetrius Poliorcetes, the son of Antigonus, wrested part of Greece from Cassander. At first Ptolemy had made a successful descent upon Asia Minor and on several of the islands of the Archipelago; but he was at length totally defeated by Demetrius at the naval Battle of Salamis.
Demetrius conquered Cyprus in 306 BC. Following the victory Antigonus assumed the title king and bestowed the same upon his son, a declaration that he was claiming to be Alexander's heir. He now prepared a large army and a formidable fleet, the command of which he gave to Demetrius, and hastened to attack Ptolemy in his own dominions. His invasion of Egypt, however, proved a failure; he was unable to penetrate Ptolemy's defences and was obliged to retire. Demetrius in 305 BC attempted the reduction of Rhodes, which had refused to assist Antigonus against Egypt. The siege of Rhodes lasted a year and ended in 304 BC when Demetrius meeting with obstinate resistance, he was obliged to make a peace treaty upon the best terms that he could.
The most powerful satraps of the empire, Cassander, Seleucus, Ptolemy and Lysimachus, responded to Antigonus's assumption of the royal title by proclaiming themselves also kings. Antigonus soon found himself at war with all four, largely because his territory shared borders with each of them. He demanded from Cassander the unconditional submission of Macedonia. Seleucus, Lysimachus and Ptolemy joined forces and attacked him. He was obliged to recall Demetrius from Greece, although he was again winning success after success there, and moved against Lysimachus. The army of father and son was defeated by the united forces of Seleucus and Lysimachus at the decisive Battle of Ipsus in 301 BC. Antigonus himself died in the battle after being struck by a javelin, in the eighty-first year of his life. Prior to Ipsus, he had never before lost a battle. With his death any plans he may have had of reuniting Alexander's Empire came to an end. The victors did not claim power over each other, but instead accepted their kingdoms as separate. Antigonus's kingdom was divided up, with most ending up in the hands of Lysimachus and Seleucus.