The Des Moines River with its tributaries is the largest river in Iowa, and the most westerly of the major rivers within the state. Watersheds contiguous to its basin on the west drain into the Missouri River.

Extends across east-central Iowa from beyond the state line on the north to the Mississippi River on the southeast. Bounded almost entirely by the Wapsipinicon River basin on the east and by the Des Moines River and Skunk River basins on the west.

Includes the Iowa portion of the drainage area of the Nodaway, Platte, Grand, Chariton, Fabius, Wyaconda, and Fox rivers and Tarkio Creek.