The biodiversity of the Southeastern United States is threatened by the combination of the high number of imperiled species and high projected human population growth in the coming decades. Conservation planning for imperiled species requires identifying the areas where efforts are most likely to avert extinction. Here we address that challenge by ranking each of the 875 counties of the Southeast using a metric based on the number of species listed under the Endangered Species Act, projected population growth through 2040, and the area of currently protected land. The analysis reveals that the counties surrounding some of the Southeast’s largest cities have the highest scores, but some areas that are currently less-developed are also of high concern because they harbor a large number of listed species. Future research can easily adapt this study’s methodology to inform conservation planning for imperiled species in other regions.