Despite improved understanding of how aquatic organisms are influenced by environmental conditions at multiple scales, we lack a coherent multiscale approach for establishing stream conservation priorities in active coal-mining regions. We classified watershed conditions at 3 hierarchical spatial scales, following a house–neighborhood–community approach, where houses (stream segments) are embedded within neighborhoods (Hydrologic Unit Code [HUC]-12 watersheds) embedded within communities (HUC-10 watersheds). We used this information to develop a framework to prioritize restoration and protection in two HUC-8 watersheds in an intensively mined region of the central Appalachians. We used landscape data to predict current conditions (water chemistry and macroinvertebrate biotic integrity) for all stream segments with boosted regression tree (BRT) analysis. Mining intensity, distance to mining, and coal type were the dominant predictors of water quality and biological integrity. A hardness–salinity dimension of the water-chemistry data was explained by land-cover features and stream elevation. We compiled segment-level conditions to the HUC-12 and HUC-10 watershed scales to represent aquatic resource conditions hierarchically across 3 watershed-management scales. This process enabled us to relate stream-segment watershed conditions to watershed conditions in the broader context, and ultimately to identify key protection and restoration priorities in a metacommunity context. Our hierarchical classification system explicitly identifies stream restoration and protection priorities within a HUC-12 watershed context, which ensures that the benefits of restoration will extend beyond the stream reach. Highest protection priorities are high-quality HUC-12 watersheds adjacent to low-quality HUC-12 watersheds. Highest restoration priorities are HUC-12 watersheds in poor–fair condition within HUC-10 watersheds of good–excellent condition, whereas lowest restoration priorities are isolated HUC-12 watersheds. In high-priority HUC-12 watersheds, stream segments with the highest restoration priority are those that maximize watershed-scale restorability. A similar process for classifying conditions and restoration priorities may be valuable in other heavily impacted regions where strategic approaches are needed to maximize watershed-scale recovery.