Sugar beets, pinto beans, sunflowers, barley, oats, corn and alfalfa hay are grown on irrigated farms in the region.
The route was an important alternative to the Bozeman Trail, which had crossed the Powder River Country, but had been closed to white settlers following Red Cloud's War.
Butch Cassidy lived near Meeteetse for a while and was arrested at the insistence of local cattle baron Otto Franc and sent to the Wyoming State Penitentiary for horse theft.
In 1942 one of the nation's ten Japanese American internment camps was located in Park County in the western part of the basin.
The alluvial strata of the Willwood and Fort Union Formations of the Bighorn Basin contain a well-documented record of the Paleocene-Eocene Thermal Maximum (PETM).