Land-use change around protected areas can reduce their effective size and limit their ability to conserve biodiversity because land-use change alters ecological processes and the ability of organisms to move freely among protected areas. The goal of our analysis was to inform conservation planning efforts for a nationwide network of protected lands by predicting future land use change. We evaluated the relative effect of three economic policy scenarios on land use surrounding the U.S. Fish and Wildlife Service's National Wildlife Refuges. We predicted changes for three land-use classes (forest/range, crop/pasture, and urban) by 2051. Our results showed an increase in forest/range lands (by 1.9% to 4.7% depending on the scenario), a decrease in crop/pasture between 15.2% and 23.1%, and a substantial increase in urban land use between 28.5% and 57.0%. The magnitude of land-use change differed strongly among different USFWS administrative regions, with the most change in the Upper Midwestern US (approximately 30%), and the Southeastern and Northeastern US (25%), and the rest of the U.S. between 15 and 20%. Among our scenarios, changes in land use were similar, with the exception of our “restricted-urban-growth” scenario, which resulted in noticeably different rates of change. This demonstrates that it will likely be difficult to influence land-use change patterns with national policies and that understanding regional land-use dynamics is critical for effective management and planning of protected lands throughout the U.S.