The Cache River begins in Butler County, Missouri and flows southwest into northeastern Arkansas. The river empties into the White River at Clarendon in east-central Arkansas.
The river is a slow muddy river with meandering channels, sloughss, swampy areas, and oxbow lakes.
The name of the river is probably a Picardie word meaning "hunt" as a reference to the abundant wildlife along the river. The first explorer into the area was Father Marquette for whom Picard was the native tongue.
The low-lying areas around the river above its confluence with the White River is a popular destination for duck hunters. The Cache River National Wildlife Refuge along the lower river is the largest remaining tract of contiguous bottomland hardwood forest found in North America. The refuge is also the most important wintering area for mallard ducks and other migratory water fowl on the continent.
The river supports 53 mammalian species, over 200 bird species, and nearly 50 species of reptiles and amphibians. The area has the only remaining population of native black bears in the state.
During the American Civil War, the Battle of Cotton Plant was fought along the Cache River at Cotton Plant, Arkansas.