Amphipolis is located at the foot of Mount Pangaion, near the banks of the River Strymon. Archaeological evidence indicates strong human presence and activity in the area from as early as the Middle Neolithic. Built like an amphitheatre at a strategic location, Amphipolis was an Athenian colony founded in 437/6 on the site of Ennea Hodoi (Nine Ways), and the earlier city of Hedonia. Public and private life in the city blossomed during the Classical and Hellenistic periods, while the fact that the Via Egnatia passed through Amphipolis was a key factor in maintaining its prosperity through Roman and early Christian times. At least until 692 it was the seat of a bishop, and grew into a major centre of ecclesiastical activity in the area. Excavations within the city limits have revealed four basilicas decorated with sumptuous mosaics and marble revetments , an episcopical palace and a centrally planned church, all dating to this period. At this time the city was fortified by a 7.5 km long wall, and a second enclosure 2.2 km in length, bounding the citadel.
 
The city was probably destroyed in the 8^th or 9^th century, for it was then that the inhabitants relocated to the major fortified harbour town of Chrysoupoli, at the mouth of the River Strymon . A small settlement named Marmarion grew up on the ruins of Amphipolis, becoming a staging post for travellers crossing the Strymon at the nearby ford of Poros Marmariou. In the 13th-14th century two towers owned by the monasteries of Mount Athos were founded on either side of the river. The better preserved of the two, built of spolia on a hill to north of the modern village, stood three storeys high and was surrounded by a defensive wall. According to an inscription, the tower was founded in 1367 by two generals named Alexius and Ioannis, blood brothers and founders of Pantocrator Monastery on Mount Athos, which owns the monument. On the opposite bank of Strymon lie the remains of the second tower, which must have been at least two floors high. Although the towers were primarily used as warehouses for storing produce grown on the local estates and monasteries, their presence also served to control the passage to the hinterland. Chrysoupoli was abandoned in the 16^th century, whereas Marmaris survived for a further two hundred years, only to be replaced by Neohorio.