Abstract The loss of biodiversity is one of the most serious environmental issues in the Anthropocene. Understanding the extinction risk of species is essential for preemptive conservation measures, but is hampered by gaps in geographical and evolutionary knowledge, especially in areas/regions that are highly diverse in species. Combined with a 21 109‐taxon angiosperm mega‐phylogeny and comprehensive species distribution database, we evaluated the characteristics of angiosperm extinction risk at the Sino‐Himalaya and the Tibetan Plateau (SHTP). Overall, our results show that there is a strong interaction between evolutionary and environmental factors on extinction risk, and both contribute spatially to threat processing in the SHTP. The extinction risk of angiosperms in this region is spatially and phylogenetically clustered; the clades with low species richness are significantly more vulnerable to extinction than species‐rich ones; the regions with the highest extinction risk are concentrated in the mountainous areas of southwest China. Integrated with the existing Red List, we further delineated more than 3000 potentially threatened species and proposed practical conservation priorities for four types of species in the SHTP. The extinction risk of angiosperms showed both phylogenetically and spatially aggregate characteristics, serving as an important reference for predicting extinction trends and the formulation of targeted conservation strategies.