In the early first millennium BC, several waves of Celts invaded Portugal from Central Europe and intermarried with local peoples, the Iberians, forming the Celt-Iberians. Early Greek explorers named the region "Ophiussa" (Greek for "land of serpents") because the natives worshiped serpents. In 238 BC, the Carthaginians occupied the Iberian coasts. In this period several small tribes occupied the territory, the main were the Lusitanians, who lived between the Douro and Tagus rivers, and the Callaeci who lived north of the Douro river among some other tribes. The Conii, of possible Phoenician origin, was established in southern Portugal for a long time. The Celtics, a later wave of Celts, settled in Alentejo.

In 219 BC, the first Roman troops invaded the Iberian Peninsula, driving the Carthaginians out in the Punic Wars. The Roman conquest of Portugal started from the south, where they found friendly natives, the Conii. Over decades, the Romans increased their sphere of control. But in 194 BC a rebellion began in the north, the Lusitanians successfully held off the Romans, took back land and ransacked Conistorgis, the Conii capital, because of their alliance with Rome. Viriathus, the Lusitanian leader, drove the Roman forces out. Rome sent numerous legions, but success was only achieved by bribing Lusitanian officials to kill their own leader. During this period, a process of Romanization was carried out, leading Lusitania to gain Latin Right in 73 AD.