Guayrá was a historical region of the Spanish Empire, located in the Governorate of the Río de la Plata, within the colonial Viceroyalty of Peru. The region is located in present-day Paraguay and Paraná.
There are some conflicting etymologies for the origin of the name, with some claiming it was named after a cacique of the region whose name was Guayrá or Guayracá. Alternatively, the word might come from Guarani "kwa y ra" ("can not pass", "impassable") or even "guay ra" ("river that goes [beyond]").
The limits of Guayrá were the Iguazu River on the south, the Paraná River on the west, the Tiete (or Añemby) River to the north, and the line of the Treaty of Tordesillas to the east. The Tiete also marked the boundary between the Tupi and Guarani Indians.
Aleixo Garcia crossed the region in 1522. In 1542, Alvar Nunez Cabeza de Vaca travelled through its southern reaches on his way to Asunción from Santa Catarina Island.
The town of Ontiveros was founded by Captain Garcia Rodriguez de Vergara on orders from Domingo Martínez de Irala in 1554. It was located on the left bank of the Paraná, between the Iguazu and Pipiri-Guazu, about 50 kilometres (31 miles) north of Salto del Guairá, in the territory of the cacique Canendiyu. It was intended to serve as a connection to Portuguese Colonial Brazil.