Amphipolis was built on a raised plateau overlooking the east bank of the river Strymon where it emerged from Lake Cercinitis, about 3 m. from the Aegean Sea.
Xerxes I of Persia passed during his invasion of Greece of 480 BC and buried alive nine young men and nine maidens as a sacrifice to the river god. Near the later site of Amphipolis Alexander I of Macedon defeated the remains of Xerxes' army in 479 BC. Throughout the 5th century BC, Athens sought to consolidate its control over Thrace, which was strategically important because of its primary materials (the gold and silver of the Pangaion hills and the dense forests essential for naval construction), and the sea routes vital for Athens' supply of grain from Scythia.
After the conquest by Philip II, the city was not immediately incorporated into the kingdom, and for some time preserved its institutions and a certain degree of autonomy. In the reign of Alexander, Amphipolis was an important naval base, and the birthplace of three of the most famous Macedonian Admirals: Nearchus, Androsthenes and Laomedon whose burial place is most likely marked by the famous lion of Amphipolis. After the final victory of Rome over Macedonia in a battle in 168 BC, Amphipolis became the capital one of the four mini-republics which were created by the Romans out of the kingdom of the Antigonids which succeeded Alexander’s Empire in Macedon.
During the period of Late Antiquity, Amphipolis benefited from the increasing economic prosperity of Macedonia, as is evidenced by the large number of Christian Churches that were built. Significantly however, these churches were built within a restricted area of the town, sheltered by the walls of the acropolis. This has been taken as evidence that the large fortified perimeter of the ancient town was no longer defendable, and that the population of the city had considerably diminished.
Philippi was established by the king of Macedon, Philip II, on the site of the Thasian colony of Krinides or Crenides, near the head of the Aegean Sea at the foot of Mt. Orbelos about 8 miles north-west of Kavalla, on the northern border of the marsh that in Antiquity covered the entire plain separating it from the Pangaion hills to the south of Greece.
The objective of founding the town was to take control of the neighbouring gold mines and to establish a garrison at a strategic passage: the site controlled the route between Amphipolis and Neapolis, part of the great royal route which crosses Macedonia from the east to the west and which was reconstructed later by the Roman Empire as the Via Egnatia. Philip II endowed the new city with important fortifications, which partially blocked the passage between the swamp and Mt. Orbelos, and sent colonists to occupy it. The discovery of new gold mines near the city, at Asyla, contributed to the wealth of the kingdom and Philip established a mint there. The city was finally fully integrated into the kingdom under Philip V.
The city reappears in the sources during the Roman civil war that followed the assassination of Julius Caesar. His heirs Mark Antony and Octavian confronted the assassins of Caesar, Marcus Junius Brutus and Cassius, at the Battle of Philippi in the plain to the west of the city during October in 42 BC. Antony and Octavian were victorious in this final battle against the partisans of the Republic.