The canyon was long suspected, but only confirmed in the 1990s, of having been used as a campsite by Francisco Vásquez de Coronado and his army twice in spring of 1541 while on his El Dorado expedition.

[4] It was on October 10, 1871, also the site of the main skirmish of Col. Ranald S. Mackenzie's initial campaign against the Plains Comanches, known as the Battle of Blanco Canyon.

[5] On this same campaign, Mackenzie established a supply camp named Anderson's Fort on a curved ridge a short distance southeast of the canyon mouth; it is now on the National Register of Historic Places.

[2] Shortly thereafter, once the Plains Indians had been forced onto reservations, the nearby site of Mount Blanco on the east rim of the canyon was established in 1877 by Henry Clay Smith and his wife, the former Elizabeth Boyle, as the first permanent white settlement on the West Texas plains, and the first post office west of Fort Griffin.

[6] Early settlers were attracted to the site for the same reason as Coronado had been - the ready supply of wood and water, which were rarities in the area.