During Classical Antiquity, Mértola was inhabited by Phoenicians, Carthaginians and finally the Romans, who called it Myrtilis Iulia.

The strategic location of Mértola, on a hill by the northernmost navigable part of the Guadiana river, was crucial in its early development.

Agricultural products grown in the villae nearby and valuable minerals (silver, gold and tin) obtained from the lower Alentejo region were sent from the fluvial port of Mértola via the Guadiana to Southern Hispania and the Mediterranean.

[4] Between 1st and 2nd century, Myrtilis was part of the larger Pacensis region (under the capital Beja/Pax Iulia) and acquired a great importance, as a dynamic commercial centre, permitting it to mint its own coin.

[5] The town was raised to the status of a Municipium in times of Emperor Augustus and was connected to important Roman cities (Beja, Évora) through a road system.