Rising in the Rocky Mountains, the river drains a sparsely populated, semi-arid watershed of 23,800 square miles (62,000 km2), ending just east of Fort Peck, Montana.

Near Malta, it turns north, then southeast, flowing past Glasgow and joining the Missouri in Valley County, Montana, 5 miles (8 km) downstream from Fort Peck Dam.

These fine-grained sediments result from the erosion of soft clay-rich rocks along the Milk River basin in southern Alberta, such as the Foremost, Oldman and Dinosaur Park formations.

[11] At the time of Lewis's exploration, the Milk River drainage was legally part of the United States as a component of the Louisiana Purchase.

The landscape consists of native grasslands, riparian cottonwood groves, badlands, coulees, cliffs, sand dunes, and rocky outcrops.