The origin of the river name is Waséoyuze, Lakota for "place where vermilion is obtained".

The East Fork, approximately 103 miles (166 km) long,[2] rises in Lake Whitewood in Kingsbury County on the Coteau des Prairies.

The West Fork, approximately 108 miles (174 km) long,[2] rises in Miner County.

Both forks flow south, roughly parallel, joining east of Parker.

The Vermillion River drains about 2,180 square miles (5,600 km2) of the southwestern edge of the Coteau des Prairies.