Key Cave NWR, about 5 miles southwest of Florence, Alabama, was established in 1997 to ensure the biological integrity of Key Cave, Collier Cave, and the aquifer common to both. Key Cave has been designated as critical habitat for the endangered Alabama cavefish (Speoplatyrhinus poulsoni) and as a priority one maternity cave for the endangered gray bat (Myotis grisescens). Collier Cave, located approximately 1.5 miles upstream from Key Cave and within the acquisition boundary, is important to both species as potential habitat. Both caves are on the northern shore of Pickwick Lake in a limestone karst area that contains numerous sinkholes and several underground cave systems. The area's sinkholes are an integral component of groundwater recharge to the caves. The area directly north of Key Cave was identified as a potential high hazard risk area for groundwater recharge and this is where the 1,060-acre Refuge was established.

Key Cave NWR is located about 5 miles southwest of Florence, Alabama. From State Route 20, turn west on Lauderdale County Route 2 (Gunwaleford Road). Follow Route 2 for about four miles and turn south on Lauderdale County Route 223 (gravel road). Follow Route 223 for about 1.5 miles and turn west on Lauderdale County Route 204 (gravel road). Follow Route 204 for 0.25 miles and the Refuge is located on the south side of the road.