The quechua-speaking Cabanas, probably descended from the Wari culture, and the Aymara-speaking Collaguas, who moved to the area from the Lake Titicaca region, inhabited the valley in the pre-Inca era. The Inca probably arrived in the Colca valley around 1320 AD, and established their dominion through marriage, rather than through warfare. The Spaniards, under Gonzalo Pizarro, arrived in 1540, and in the 1570s the Spanish viceroy Francisco de Toledo ordered the inhabitants to leave their scattered settlements and to move to a series of centrally-located pueblos, which remain the principal towns of the valley. Franciscan missionaries built the first chapel in the valley in 1565, and the first church in 1569 (Coporaque).

No passable roads existed between Arequipa and Chivay until the 1940s, when a road was completed to serve the silver and copper mines of the region. In the 1970s and 1980s, the Majes Hydroelectric Project — which diverted water from the Colca River to irrigate crops in the Majes region — built roads within the valley, and opened the area to outsiders. Access today is usually vía Arequipa.

In May 1981, the Polish “Canoandes” rafting expedition made the first descent of the river below Cabanaconde, and proclaimed the possibility of its being the world’s deepest canyon. It was so recognized by the Guinness Book of Records in 1986, and a National Geographic article in January 1993 repeated the claim. The joint Polish/Peruvian “Cañon del Colca 2005″ expedition verified the altitudes of the river and the surrounding heights via GPS in 2005.

Tourism has exploded since the publicity of the 1980s and 1990s, increasing from a few thousand visitors annually, to nearly 150,000 visitors in 2010.

El Virrey Toledo aplica la Reducción de Indios y esta vasta población es obligada a sangre y fuego a reducirse en pueblos. Hasta ese momento toda la población se dedicaba a las tareas agrícolas o ganaderas y vivían en pequeños caceríos diseminados a lo largo del valle en lugares bien ubicados para cumplir con sus labores.