Changes in forest ecosystem function and condition arise from changes in forest fragmentation. Previous studies estimated forest fragmentation for the continental United States (US). In this study, new temporal land-cover data from the National Land Cover Database (NLCD) were used to estimate changes in forest fragmentation at multiple scales for the continental US. Early and late dates for the land-cover change data were ca. 1992 and ca. 2001. Forest density was used as a multi-scale index of fragmentation by measuring the proportion of forest in neighborhoods ranging in size from 2.25 to 5314.41 ha. The multi-scale forest density maps were classified using thresholds of 40% (patch), 60% (dominant), and 90% (interior) to analyze temporal change of fragmentation. The loss of dominant and interior forest showed distinct scale effects, whereas loss of patch forest was much less scale-dependent. Dominant forest loss doubled from the smallest to the largest spatial scale, while interior forest loss increased by approximately 80% from the smallest to the second largest spatial scale, then decreased somewhat. At the largest spatial scale, losses of dominant and interior forest were 5 and 10%, respectively, of their ca. 1992 amounts. In contrast, patch forest loss increased by only 25% from the smallest to largest spatial scale. These results indicate that continental US forests were sensitive to forest loss because of their already fragmented state. Forest loss would have had to occur in an unlikely spatial pattern in order to avoid the proportionately greater impact on dominant and interior forest at larger spatial scales.