Several archaeological sites near the Cactus Park turnoff were excavated by archaeologists from the University of Colorado and Denver Museum of Natural History in 1951 and 1952. One of these sites, on private land, revealed deposits of over 15 feet and showed a long record of human use. Artifacts collected here include projectile points, knives, scrapers, milling stones, bone awls, tubular bone beads and bone from mule deer and rabbits. Fire hearths, made of stone and in shallow pits, and some lined storage pits were also found. These sites demonstrate the concentrated use of the Canyon over a long period of time.

Much of Colorado was once home to the Ute Indians. Painted rock art (pictographs) of the Ute Indians, painted between 1500 and 1800, is often found in association with the older petroglyphs. The Utes used the area now covered by the Byway as a travel route to access the Uncompahgre Plateau and adjacent river valleys. The Ute Indian name"Tabeguache" means "place where the snow melts first," and probably referred to the entire Plateau.

As white settlers moved into Colorado and their demands for the mineral and agricultural resources of the area increased, the U.S. Government made a series of treaties with the Utes, reducing their territory with each treaty. In the 1880s, the Ute tribes were moved to reservations in Utah and Southwestern Colorado, a considerable distance from this area, where they reside today.