The Mission of Nahuel Huapi was an intermittent Jesuit mission that existed in colonial times on the shores of Nahuel Huapi Lake, northern Patagonia. The exact location of the missions are not known but it has been suggested, based on a Christian grave finding, that the mission of the early 18th century was located in Huemul Peninsula.
The Mission of Nahuel Huapi depended on administrative and religious matters on the Governorate of Chiloé but was nevertheless financed from the city of Valdivia. Historian Gabriel Guarda do however disagree claiming the mission was whithin the jurisdiction of Valdivia.
Nahuel Huapi lake was known to Spaniards since the times of the Conquest of Chile. In the summer of 1552–1553, the Governor of Chile Pedro de Valdivia sent Francisco de Villagra to explore the area east of the Andes at the latitudes of the city of Valdivia. Francisco de Villagra crossed the Andes through Mamuil Malal Pass and headed south until reaching Limay River in the vicinity of Nahuel Huapi Lake.
Another early Spaniard to visit the zone of Nahuel Huapi Lake was the Jesuit priest Diego de Rosales. He had been ordered to the area by the Governor of Chile Francisco Antonio de Acuña Cabrera y Bayona, who was concerned about the unrest of the native Puelche and Poya after the slave-hunting expeditions carried out by Luis Ponce de León in 1649, who captured Indians and sold them into slavery. Diego de Rosales started his journey at the ruins of Villarica in Chile, crossed the Andes through Mamuil Malal Pass, and traveled further south along the eastern Andean valleys, reaching Nahuel Huapi Lake in 1650.