The river was the primary route for white settlers including Amos Graham and Isaac Hogan following the Platte Purchase of 1836 which opened northwest Missouri for settlement.

The West Nodaway River rises northeast of Massena in eastern Cass County, Iowa, and flows 73.8 miles (118.8 km)[2] south-southwest past Villisca and Clarinda, the largest town on the river, to its junction with the East Nodaway.

Continuing from the Iowa border in Nodaway County, Missouri, the river travels south a mile west of Burlington Junction where it intersects US 136.

Continuing southerly, the river passes west of Quitman and east of Bilby Ranch Lake Conservation Area before crossing Missouri Route 46.

Continuing southerly, it passes between Maitland to its east and Graham to its west, and reaches the tripoint with Andrew County.