To augment mammal conservation in the Eastern Himalayan region, we assessed the resident 255 terrestrial mammal species and identified the 50 most threatened species based on conservation status, endemism, range size, and evolutionary distinctiveness. By using the spatial analysis package letsR and the complementarity core-area method in the conservation planning software Zonation, we assessed the current efficacy of their protection and identified priority conservation areas by comparing protected areas (PAs), land cover, and global ecoregion 2017 maps at a 100 × 100 m spatial scale. The 50 species that were most threatened, geographically restricted, and evolutionarily distinct faced a greater extinction risk than globally non-threatened and wide-ranging species and species with several close relatives. Small, medium-sized, and data-deficient species faced extinction from inadequate protection in PAs relative to wide-ranging charismatic species. There was a mismatch between current PA distribution and priority areas for conservation of the 50 most endangered species. To protect these species, the skewed regional PA distribution would require expansion. Where possible, new PAs and trans-boundary reserves in the 35 priority areas we identified should be established. There are adequate remaining natural areas in which to expand current Eastern Himalayan PAs. Consolidation and expansion of PAs in the EH requires strengthening national and regional trans-boundary collaboration, formulating comprehensive regional land-use plans, diversifying conservation funding, and enhancing information sharing through a consolidated regional database.