It issues from the lake in Hendricks, Minnesota, and flows northeastwardly through northwestern Lincoln County as an intermittent stream on the Coteau des Prairies, a morainic plateau dividing the Mississippi and Missouri River watersheds, into western Yellow Medicine County, where it flows off the Coteau, dropping 250 feet (76 m) in eight miles (13 km).

Continuing northeastwardly through flat till plains with occasional willows and cottonwoods along its banks, the river flows into eastern Lac qui Parle County, passing to the east of Dawson.

[4][8][9] The river's largest tributary, the West Branch Lac qui Parle River,[10] 64.1 miles (103.2 km) long,[11] rises on the coteau in eastern Deuel County, South Dakota, and flows initially northeastwardly as an intermittent stream, past Gary, South Dakota, then eastwardly through Lac qui Parle County, past Dawson.

Other tributaries include two small trout streams: Canby Creek, 24 miles (39 km) long, which flows northeastwardly on the Coteau in western Yellow Medicine County, through Canby; and Tenmile Creek, 33 miles (53 km) long, which flows eastward and northwardy through Lac qui Parle County, through Boyd.

[14] Calcerous fens are calcium-rich peat wetlands which support endangered plants in Minnesota like the cut-leaf water parsnip and hairy fimbry.