Cuyo, historical region, western Argentina, roughly comprising the modern provinces of Mendoza, San Juan, and San Luis in the Andean piedmont. Its first European visitor was the Spanish adventurer Francisco de Villagrá in 1551; and the Cuyo later became the first area of permanent interior settlement in what now is Argentina. It is partially separated from the Pampa to the southeast by the Sierra de Córdoba, a low range of mountains extending along a north–south axis west of the city of Córdoba.
Mendoza is the largest city in the Cuyo; founded in the 16th century, it was destroyed by earthquake in its third centennial year (1861) and was rebuilt with extraordinarily wide streets and solid buildings as a precaution against further disaster. The small city of San Juan also suffered from major earthquakes in 1944 and 1977. While the area is known for violent natural phenomena, it has a flourishing economy based on the irrigated cultivation of grapes, fruits, and vegetables in San Juan and Mendoza provinces and the exploitation of petroleum, natural gas, copper, lead, and uranium.