These ancient Indians inhabited the rim and inner canyon, surviving by hunting and gathering along with some limited agriculture. Later the Cohonina tribe lived west of what is now the current site of Grand Canyon Village. However by the late 13th century, both tribes had moved on, most likely due to drought.

For approximately one hundred years the canyon area was uninhabited by humans. Paiutes from the east and Cerbat from the west were the first humans to reestablish settlements in and around the Grand Canyon. The Paiute settled the plateaus north of the Colorado River and the Cerbat built their communities south of the river, on the Coconino Plateau. Sometime in the 15th century the Navajo, or the Dine, arrived in the area.

The first documented case of Europeans viewing the Grand Canyon occurred in September of 1540. That year Hopi guides led a group of 13 Spanish soldiers under Captain Garcia Lopez de Cardenas to find the fabled Seven Cities of Cibola for his superior officer, the conquistador Francisco Vasquez de Coronado.

The group arrived at South Rim of the Grand Canyon between Desert View and Moran Point and saw a river below. Pablo de Melgrossa, Juan Galeras and a third soldier descended one third of the way into the Canyon until they were forced to return because of lack of water. It is speculated that their Hopi guides must have been reluctant to lead them to the river, as they surely knew the route to the canyon floor.

Failing in their attempts to find gold, the Spaniards soon left the area and it would be more than two centuries before it was once again visited by Europeans.

In 1776, Fathers Francisco Atanasio Dominguez and Silvestre Velez de Escalante traveled with a group of Spanish soldiers to explore southern Utah. One their journey the group traveled along the North Rim of the Canyon in Glen and Marble Canyons in search of a route from Santa Fe, New Mexico, to Monterey, California.