The refuge is also the most important wintering area for mallard ducks and other migratory waterfowl on the continent.

As a result, low-lying areas in the vicinity of the river's lower course are a popular destination for duck hunters.

[4] The watershed also contains the largest remaining tract of contiguous bottomland hardwood forest found in North America.

Because of these combination of these unique features, the Cache River National Wildlife Refuge was created along approximately 90 miles (140 km) along the river's lower reaches this location was also used by team trees to plant 20 million trees.

[5] The Cache is formed by a confluence of agricultural ditches in Butler County, Missouri and soon enters Arkansas, flowing generally south-southwestwardly.