St. Catherine Creek National Wildlife Refuge was established in January 1990 to preserve, improve and create habitat for waterfowl. Intensive management programs on the refuge provide excellent winter habitat and resting areas for waterfowl in the Lower Mississippi River Valley. Encompassing nearly 26,000 acres, with a potential size of 34,256 acres, the refuge is located in Adams County in southwest Mississippi. The headquarters lies 13 miles south of Natchez, Mississippi. Natchez is the oldest settlement on the Mississippi River and is world renowned for its beautiful antebellum homes. The western refuge boundary is formed by the Mississippi River. The eastern boundary meanders along the loessal bluffs and the southern boundary borders the Homochitto River.

St. Catherine Creek National Wildlife Refuge headquarters is located 13 miles south of Natchez, Mississippi. From Natchez, follow U.S. Highway 61 South approximately 10 miles to Sibley. Turn right and follow York Road 2 miles to the refuge entrance. Turn left on Pintail Lane. The headquarters is located approximately 0.7 miles down Pintail Lane on the right. Refuge directional signs are located at each turn.