Countries in eastern Africa have set aside significant proportions of their land for protection. But are these areas representative of the diverse range of species and habitats found in the region? And do conservation efforts include areas where the state of biodiversity is likely to deteriorate without further interventions? Various studies have addressed these questions at global and continental scales. However, meaningful conservation decisions are required at finer geographical scales. To operate more effectively at the national level, finer scale baseline data on species and on higher levels of biological organization such as the eco-regions are required, among other factors. Here we adopted a recently developed high-resolution potential natural vegetation (PNV) map for eastern Africa as a baseline to more effectively identify conservation priorities. We examined how well different potential natural vegetations (PNVs) are represented in the protected area (PA) network of eastern Africa and used a multivariate environmental similarity index to evaluate biases in PA versus PNV coverage. We additionally overlaid data of anthropogenic factors that potentially influence the natural vegetation to assess the level of threat to different PNVs. Our results indicate substantial differences in the conservation status of PNVs. In addition, particular PNVs in which biodiversity protection and ecological functions are at risk due to human influences are revealed. The data and approach presented here provide a step forward in developing more transparent and better informed translation from global priorities to regional or national implementation in eastern Africa, and are valid for other geographic regions.