The Great River National Wildlife Refuge protects approximately 11,600 acres along 120 miles of the Mississippi River, stretching north of St. Louis, Missouri. Three separate units are located in the floodplain, on both the Illinois and Missouri sides of the river. In 1998, the Great River Refuge was designated as a globally important bird area, due to its value to shorebirds, songbirds, and waterfowl. The refuge's proximity to St. Louis provides excellent educational opportunities to a large population. The Clarence Cannon National Wildlife Refuge is also under the administration of the Great River Refuge. Great River Refuge, in turn, is part of the Mark Twain National Wildlife Refuge complex, which also includes Port Louisa, Two Rivers, and Middle Mississippi River refuges. The complex headquarters is in Quincy, Illinois.

The headquarters for the Great River Refuge is located on the Clarence Cannon Refuge. From St. Louis, take I-70 west and take exit Highway 79 north. Take 79 north approximately 35 miles to the town of Annada. Turn right on County Road 206 and proceed one mile to the refuge office.