Its lower 20 miles (32 km) flows through Glen Canyon National Recreation Area, where it finally disembogues into the Colorado River at a point that is now submerged beneath Lake Powell.

The canyon carved by the river is particularly isolated and seldom visited compared to other natural areas in the region.

[6] The outlaw Butch Cassidy and his gang used tributary canyons of the Dirty Devil, such as Robbers Roost, as a hideout in the 1890s.

The United States Bureau of Reclamation drew up a plan to reduce the salinity of the Dirty Devil River by collecting salty spring water and using deep-well injection to dispose of it.

It is also spanned by a bridge on State Route 24 a few miles NE of Hanksville, UT, just downstream from the confluence of Muddy Creek and the Fremont river.