Plants, animals, and Native Americans were the first inhabitants of the Grand Canyon. Pueblo Indians lived in Northeast Arizona between 200 BC and 1300 AD. Zuni tribes currently abide in New Mexico, but they believe they originate from the Grand Canyon. Presently, Hopi people live in the inner canyon west of the Grand Canyon Village. There is a Navajo reservation on the eastern park border, and a Hualapai reservation located on the southern border of the park. Also, Southern Paiute Indians inhabit territory north of the Colorado River.

The Grand Canyon supports a diverse plant and animal population. It contains seventy-five mammal species, fifty species of reptiles, twenty-five types of fish and over three hundred bird species. There are also a few endangered and threatened species in the region, including the Colorado River fish, the peregrine falcon, the bald eagle, and numerous endangered plants.

Europeans and pioneers eventually made their way to the Grand Canyon. The first European to see the canyon was Spanish explorer Francisco Vasquez de Cornado in 1540. The first known account of the first passage of the Colorado River through the Grand Canyon was accomplished by Major John Wesley Powell in 1869. He was a Civil War veteran with only one arm and managed to successfully navigate nine men through the bottom of the canyon on four crude wooden boats.

During the early nineteenth century, people became interested in the area for its mining prospects, especially in copper and asbestos. The first pioneers settled along the rim in the 1880's. In 1893, the region was granted federal protection as a forest reserve. It later became a national monument. The popularity of tourism exceeded mining by the early 1900's. In 1901, a railroad line was extended to the South Rim from Williams, Arizona. Due to the increase in tourism, the El Tovar Hotel was built in 1905. Not until 1919 did the Grand Canyon receive national park status. Today, five million people a year visit this natural marvel.