The Cache River National Wildlife Refuge is a 55,000 acre wildlife refuge in the state of Arkansas managed by the United States Fish and Wildlife Service.

The Cache River National Wildlife Refuge runs along the flood-plain of the Cache River for 70 miles from the Cache River's mouth at Clarendon, Arkansas to the town of Grubbs, Arkansas. The refuge encompasses land in the Arkansas counties of Jackson, Woodruff, Prairie, and Monroe.

The refuge has been recognized as a Wetland of International Importance, it is also the most important wintering area for ducks and the largest remaining tract of contiguous bottomland hardwood forest on the North American continent.

The refuge includes 33,000 acres of bottomland forest and sloughss. It also includes several oxbow lakes, as well as 4,300 acres of croplands and 7,500 acres of reforested areas.

The refuge is home to over 50 species of mammals including deer, raccoon, bobcat, and river otter. It also is home for nearly 240 species of birds including ducks, geese, wading birds, and other assorted migratory birds. The swampy bottomlands are also home to 48 species of reptiles and amphibians.

Since the establishment of the refuge in 1986 private land prices adjacent to the refuge have more than doubled. The refuge continues to grow as land is acquired on a "willing seller" basis over time.

Other protected areas for wildlife co-exist with the Cache River National Wildlife Refuge along the Cache and White Riverss including the Bald Knob National Wildlife Refuge, the Hurricane Lake State Wildlife Management Area.