Clarence Cannon National Wildlife Refuge was established in 1964 with funds from the purchase of migratory waterfowl stamps. It lies in Pike County, Missouri, Pool 25 about one mile east of the small town of Annada, Missouri. 

The refuge was named in honor of Congressman Clarence Cannon who was influential in establishing the refuge. The area was formerly part of an agricultural levee district and all but a few hundred acres is encompassed by a levee. This National Wildlife Refuge covering 3,750 acres of Mississippi River floodplain, was established to provide a feeding and resting area for migratory birds. The refuge is located in the floodplain of the Mississippi river and is comprised of managed moist soil units, open water, wet meadows and bottomland forest habitats.

The Clarence Cannon National Wildlife Refuge office is also the headquarters for the Great River National Wildlife Refuge.