The first influence of Greek culture in Macedon came from the colonies along the shore founded in the 8th cent. B.C. and after; they had ties to their mother cities that tended to isolate them politically from Macedon. By the 7th cent. B.C. there was developing in W Macedon a political unit led by a Greek-speaking family, which assumed the title of king and aggrandized itself. Macedon was a Persian tributary in 500 B.C. but took no real part in the Persian Wars.

Alexander I (d. 450 B.C.) was the first Macedonian king to enter into Greek politics; he began a policy of imitating features of Greek civilization. For the next century the Hellenic influences grew and the state became stronger. With Philip II (reigned 359–336 B.C.) these processes reached their culmination, for by annexing Upper Macedon, Chalcidice, and Thrace he made himself the strongest power in Greece; then he became its ruler. He created an excellent army with which his son, Alexander the Great, forged his empire. That empire, although it was a Macedonian conquest, was a personal creation.

The Macedonian generals carved the empire up after Alexander's death (323 B.C.); these were the successors (the Diadochi), founders of states and dynasties—notably Antipater, Perdiccas, Ptolemy I, Seleucus I, Antigonus I, and Lysimachus. They had armies largely Macedonian and Greek in personnel, and most of them founded cities with colonies of their soldiers. Thus began the remarkable spread of the Hellenistic (Greek, rather than Macedonian) civilization. All these armies constituted a fatal drain on the population of Macedon. Macedon, with Greece as a dependency, was one of the states carved out of the Alexandrian empire. Almost immediately, however, there was struggle for the hold over Greece and even over Macedon itself. Cassander took (319–316 B.C.) Macedon and held it until his death (297); he refounded Salonica (now Thessaloníki). After a period of short-lived attempts by Demetrius I, Pyrrhus of Epirus, Lysimachus, and others to hold Macedon, Antigonus II established himself as king. He fought off the Galatian invaders and used his long reign (277–239 B.C.) to restore Macedon economically. There was constant trouble with the Greek city-states; many of them regained independence, but Antigonus III (reigned 229–221 B.C.), another strong king, reestablished Macedonian hegemony.

Under Antigonus III's successor, Philip V (reigned 221–179 B.C.), Macedon engaged in war against Rome. Although the First Macedonian War (215–205 B.C.) ended favorably for Philip, he was decisively defeated in the Second Macedonian War (200–197 B.C.), was forced to give up most of his fleet and pay a large indemnity, and was confined to Macedonia proper. By collaborating with the Romans, however, he was able to reduce the indemnity. His successor, Perseus (reigned 179–168 B.C.), foolishly aroused Roman fears and lost his kingdom in the Third Macedonian War (171–168 B.C.). Now Rome divided Macedon into four republics. Later (150–148 B.C.) a pretender, Andriscus, tried to revive a Macedonian kingdom. This time Macedonia was annexed to Roman territory and became (146 B.C.) the first Roman province. It never again had political importance in ancient times.