The role of harbors and port cities in ancient Mediterranean commerce explains patterns of urbanization and cultural exchange that are not visible if one focuses only on land routes and inland centers.

The Mediterranean's geography privileged maritime over overland trade by a factor that ancient sources quantified: moving a ton of goods by sea cost roughly 1/30th as much as moving the same ton overland, because a single ship could carry what hundreds of pack animals could, and ships needed no feeding during the voyage. The practical result was that major trading cities were coastal: Alexandria, Carthage, Corinth, Syracuse, Massalia (Marseilles), Ostia (Rome's port).

The harbor infrastructure of major ancient ports was itself impressive: the great harbor of Alexandria with its lighthouse (one of the Seven Wonders), the double harbors of Carthage (one commercial, one military), the harbor of Delos which served as the eastern Mediterranean's main entrepot in the Hellenistic period. The archaeology of ancient harbors — difficult because ancient ports are often underwater — has revealed wooden dock structures, warehouses, and the physical infrastructure of ancient commercial life.

Delos in the 2nd and 1st centuries BC was the center of the slave trade as well as the commodity trade: ancient sources claim that 10,000 slaves changed hands there in a single day, a figure that is probably exaggerated but reflects the scale of operations. The cosmopolitan merchant communities of ancient Delos — Italians, Greeks, Phoenicians, Jews, Egyptians — lived in separate residential quarters but interacted commercially and sometimes religiously.