It rises in northwestern Nebraska, in the Pine Ridgeescarpment north of Harrison, at an altitude of 4,800 ft (1,463 m). It flows SE then NE past Fort Robinson and north of Crawford. It crosses into southwestern South Dakota and flows north across the Pine Ridge Indian Reservation, then northeast, receiving Wounded Knee Creek and flowing between units of Badlands National Park. At the northern edge of the reservation it flows ENE and SE, forming the northern boundary of the reservation and the southern boundary of Buffalo Gap National Grassland. It receives the Little White River approximately 15 mi (25 km) south of Murdo, and flows E and to join the Missouri in Lake Francis Case approximately 15 mi (25 km) southwest of Chamberlain. The lower 10 mi (16 km) of the river form of an arm of the reservoir.
The river drains an area of approximately 10,200 sq mi (26,400 km²). The river bed is noted for deposits of manganese.
