The Jesuit reduction of Santa María la Mayor was founded in 1626, and by 1744 it held a population of 993. It was abandoned after the Jesuits were expelled from the Spanish colonies in 1767 after suppression of the order by the Spanish and Portuguese governments.
In 1984 the ruins of the reduction were declared a World Heritage Site by UNESCO, together with three other reductions in the area of Argentina and one in Brazil, all formerly part of the Province of Paraguay during the colonial era. The ruins have been grown over by vegetation. They are not as well preserved as those of San Ignacio Miní, also in Misiones.