It rises in the Medicine Bow Mountains, northwest of Medicine Bow Peak in southeastern Carbon County. It flows north, past Elk Mountain, then northeast, then northwest past the town of Medicine Bow and between the Shirley Mountains to the north and the Medicine Bow Mountains to the south. Near the town of Medicine Bow the Medicine Bow River is joined by its two largest tributaries Rock Creek (Wyoming), and the Little Medicine Bow River. It joins the North Platte in the Seminoe Reservoir, with the lower 10 mi (16 km) of the river forming an arm of the reservoir.
|Yearly mean discharge||year||176cf/s|
|Month with highest mean discharge||June||648cf/s|
|Month with lowest mean discharge||January||32.2cf/s|