[6] It flows east, through the Standing Rock Indian Reservation and joins the Missouri in Lake Oahe, approximately 2 mi (3 km) northwest of Mobridge.

It is the northernmost of South Dakota's major West River streams: the Grand, Moreau, Cheyenne, Bad, and White.

Draining about 5,200 square miles (13,000 km2) of the northern plateaus of the state, the Grand receives most of its water from snowmelt.

Sitting Bull (1831–1890), a Hunkpapa Lakota holy man who led his people as a tribal chief, was born on the Grand River in or nearby Dakota Territory.

The forks of the Grand was the site of a noted 1823 attack by a grizzly bear on frontiersman Hugh Glass, the inspiration for the 2015 film The Revenant.