Southern Appalachian forests are predominantly interior because they are spatially extensive with little disturbance imposed by other uses of the land. Appalachian mountaintop mining increased substantially during the 1990s, posing a threat to the interior character of the forest. We used spatial convolution to identify interior forest at multiple scales on circa 1992 and 2001 land-cover maps of the Southern Appalachians. Our analyses show that interior forest loss was 1.75–5.0 times greater than the direct forest loss attributable to mountaintop mining. Mountaintop mining in the southern Appalachians has reduced forest interior area more extensively than the reduction that would be expected based on changes in overall forest area alone. The loss of Southern Appalachian interior forest is of global significance because of the worldwide rarity of large expanses of temperate deciduous forest.