In 315 BC Cassander founded at the mouth of the Thermaic Gulf the city which was to become the third capital of the Macedonian kingdom, giving it the name of his wife Thessalonike, Alexander III's half-sister.
There are traces that the region was inhabited from the Neolithic period onwards (Karabournaki, Ano Toumba, Stavroupoli and others). There also remain architectural members of a large Ionic temple of the end of the 6th century BC, perhaps from the earlier settlement of Therme.
The Hellenistic city resulted from the forced resettlement of the inhabitants of 26 earlier settlements of the area. It was laid out according to the Hippodameian system and fortified by an extensive acropolis and walls. Following the defeat of Perseus at Pydna (168 BC), the city became the capital of the Second of the four 'merides' (portions) into which the Romans divided Macedonia.
Situated at a pivotal junction of the road network, the city became the most populous administrative and financial centre of the Province of Macedonia in the mid-2nd century AD. One of the founding members of the 'Panhellenion' -- instituted in 132/131 AD by the emperor Hadrian -- Thessalonike bore the honorific titles of 'Metropolis' and 'Koloneia', and was accorded administrative privileges. It was also the venue of the Pythian games, which took place every four years and attracted participants from all over Greece. The city flourished under Galerius, who made it his seat. Under Constantine the Great Thessalonike acquired also an artificial harbour.