Although little is known about the early prehistory of the area, most investigators assume that a sequence of human occupancy began prior to AD 1 and included desert archaic and basket maker cultures. For a period of several hundred years centered around 1100, both Kayenta and Fremont agricultural peoples occupied the area. The abandonment of a large Kayenta Anasazi village at Boulder in approximately 1275 ended the most significant period of prehistory. The village is presently part of Anasazi State Park. Hopi peoples apparently visited and hunted in the region for a period of 200 to 300 years. In the 1500's, Southern Paiutes began to visit the area and then occupied the region to historic times.
The Escalante River is generally considered to be the last major river to be "discovered" in the contiguous United States. In 1866 Captain James Andrus led a group of cavalrymen into the headwater benches of the Escalante River near the present community of Escalante. This is the first record of Anglo presence in the region. Members of the first and second Powell Expeditions did not find the mouth of the Escalante River when they passed through Glen Canyon in 1869 and 1871. The second Powell Expedition enlisted Jacob Hamblin of Kanab, Utah to re-supply the expedition at the mouth of the Dirty Devil River. Hamblin mistook the Escalante River for the Dirty Devil. Thus, in 1871 Hamblin became the first Anglo to travel through the Escalante River Canyon.
In 1872, John Wesley Powell sent the Almon Harris Thomson-Fredric S. Dellenbaugh party to the mouth of the Dirty Devil River to recover a cached boat. Upon climbing the escarpment above Pine Creek and the present community of Escalante, the party realized that the canyon was not the canyon of the Dirty Devil River. Thompson credited the party with the formal discovery of the river. Thompson named it the Escalante River and the surrounding country the Escalante Basin in honor of the Friar Silvester Valez de Escalante expedition of 1776. Many of the place names in the region were given by Thompson during further survey work in 1872, 1874, and 1875. Thompson was the first to explore some of the tributary canyons in the area. In 1875 he visited Boulder Creek and Harris Wash.
The two main communities in the area, Escalante and Boulder were settled in 1875 and 1889 respectively. Stockmen from Escalante immediately began to explore the canyon and benches in 1876. Stockmen from Boulder used the eastern portion of the region as early as 1887. Many of the canyons and benches in the area were named by or for livestockmen such as Llwellyn Harris, Ruben Collet, Sam Sheffield, John King, Charley Haymaker, Washington Phipps, William Spencer, John Moody, and Will Bowns to name a few.
Since historic times, the Escalante River Canyons have been a major barrier to east-west vehicular travel in the region. The river is presently bridged only at it's upper end. Much of the history and the present recreation access to the area is associated with early attempts to pioneer routes across the river and through the canyons. In 1879-80, the Hole-in-the-Rock expedition purposefully avoided the canyon and established the Hole in the Rock Trail along the western edge of the basin. In 1880, Charles Hall explored an alternative to the Hole-in-the-Rock Trail which crossed the lower portion at Spencer Flat, and the sand slide above the Escalante River then followed the Escalante River and Silver Falls Canyons. In 1881, Hall pioneered the Harris Wash-Silver Falls Canyon wagon route. This route was upgraded in 1920 when the Ohio Drilling Company built a road along the route to Wagon Box Mesa. The road was reopened in the late 1940's and maintained annually by Garfield County in the 1950' and 1960's The road is presently closed to all but foot and horse traffic.
In the upper portion of the basin, much of the history is associated with attempts to establish more direct routes across the rugged broken country between Escalante and Boulder which would avoid the higher elevations of the Aquarius Plateau. These abandoned roads and trails are now significant historical recreation resources and some are still in use by hikers and cattlemen. The Old Boynton road crossed the Escalante River at Slickrock Saddle Bench and was used between 1909 to 1911. The Boulder Mail Trail or Death Hollow Trail was used from 1902 to 1924. The Mail Trail avoided the Escalante River by crossing Antone Flat and Death Hollow. The Old Boulder road is the antecedent to the present Highway 12 route and much of the old road is still visible today. Although variations of this route were established, the Escalante River was not bridged until 1935. Because of this, Boulder is often cited as one of the last communities in the United Stated to gain automobile access. Final construction of the present Highway 12 was completed in 1940. The road was not completely paved until 1971. The portion of Highway 12 between Escalante and Boulder is one of the most scenic roads in the entire country.
Although the upper canyons of the Escalante River were formally reserved as the Aquarius National Forest in 1903, formal recognition of the area's recreation and scenic qualities occurred much later in the 1930's. In 1936 the Department of the Interior proposed the creation of the Escalante National Monument along the Colorado and Green rivers. The western edge of the proposal only included only the lower portion of the Escalante River. In 1937 Capitol Reef National Monument was established in the area northeast of the Escalante Canyons along the upper portion of Waterpocket Fold.
The first significant recognition of the recreational resources of the Escalante River occurred in 1941, when the National Park Service studied the basin in conjunction with a comprehensive study of water resources in the Colorado River Basin. The study was published in 1946 and identified the Aquarius Plateau-Escalante River basin as "a little known, but potentially important recreation area." It was during this period that the Escalante River-Waterpocket Fold area also began to be recognized as the strategic link between the National Parks in southwestern Utah and the canyon country of southeastern Utah, as well as a great recreation destination in it's own right.