Because of European diseases and enslavement of the indigenous Maina and other ethnic groups, the population of Borja and its vicinity declined from about 3,000 in 1638 to a few hundred by the late 18th century.

The first Spaniard known to have been in the Borja region was Juan de Salinas y Loyola who came this way in 1557, floating down the Marañón River through the tumultuous waters of the Pongo de Manseriche, a water gap, that marks the end of the Andes highlands and the beginning of the flat, forested upper Amazon Basin.

The site of Borja is 2 km (1.2 miles) past the Pongo and was inhabited at that time by the Mainas people, one of many ethnic groups living in the region.

[4][5] When Jesuit missionaries arrived in 1638 the population consisted of about 2,800 Maina and other ethnic groups and about 200 Spaniards, including a small military garrison.

Links with the highland areas of Peru were often through the town of Jaen, 210 km (130 miles) southwest in straight line distance.