Sebastián Cabot, in the service of a group of merchants of Sevilla, set out with an expedition to reach the Moluccas but was diverted into the Río de la Plata while searching for a passage to the east. The expedition passed up the Paraná and Paraguay Rivers and founded a short-lived settlement, which Indians, having suffered punitive expeditions, destroyed.
Mendoza founded Buenos Aires (Santa María de Buenos Aires) on the estuary of the Río de la Plata. The Indian population became increasingly hostile. Juan de Ayola and Domingo de Irala led explorations up the Paraná and Paraguay.
Abandoning Buenos Aires, Juan Salazar de Espinoza led colonists up to the Paraná and Paraguay and founded Asunción. Spaniards established strong ties with Guaraní Indians, adopting many of their customs. Mendoza died on his way to Spain, and colonists elected Irala as governor.
The crown named Alvar Núñez Cabeza de Vaca to replace Mendoza. He reached Asunción with more colonists and encountered opposition from Irala, who again became governor and was confirmed by the crown.
