This very old city had been contacted by Phoenicians, Greeks and Carthaginians. The foundation of the city of Santarém relates to Greco-Roman and Christian mythology, recognizing in the names of Habis and Irene, their mythical origins. The first documented traces of human occupation date back to the 8th century BC.

The population of the village would have collaborated with the Roman colonizers, when they arrived in the city in 138 BC. During this period it became the main commercial warehouse of the middle Tagus and one of the most important administrative centers of the Lusitania province. From the Romans it was named Escálabis or Scallabi castro (original Latin names: Scallabis or Scalaphium castrum). The city was the seat of a convent.

With the invasions of the Alanos and the Vandals, it became known as Santa Iria, from which the current name Santarém was later derived.

It passed into the possession of the Moors in 715, until D. Afonso Henriques finally conquered it on March 15, 1147, in an audacious blow, perpetrated during the night with a small army gathered by the King of Portugal. For a brief period before this conquest, the city was home to a small independent emirate: Taifa de Santarém.

The city was the scene of countless Cortes, but it was losing importance to Lisbon, on the coast, which later became the seat of the diocese.