China’s southwest mountainous region is one of the hotspots of biodiversity in the world. However, the study on the pattern of species richness distribution of endemic plants in this region and its influencing factors is still in the exploration stage. A clear regional spatial distribution pattern of plants and its influencing factors are very important for the protection and management of plant diversity in southwest China. In this study, 511 county-level regions in the southwest mountainous region were taken as examples to establish a plant species resource bank in the southwest mountainous region, and the distribution pattern of the proportion and abundance of endemic plant families and genera was analyzed based on 19 climate and environmental factors and 8 human disturbance factors in the southwest mountainous region. The geographical weighted regression model (GWR) was used to reveal the main factors affecting the spatial distribution of species. The results showed that: (1) A total of 4688 species investigated in the southwest mountain belong to 19 families and 32 genera. (2) The endemic species richness in the southwest mountainous region showed a significant uneven spatial pattern, mainly concentrated in the Heng Duan Mountain area, southwest Sichuan and northern Yunnan area, and the Ruoergai-Hongyuan area of West Sichuan Plateau. (3) The results of the GWR model showed that the diurnal mean temperature range, precipitation seasonality and distance from the main road had significant effects on species richness. The study on the distribution of endemic genera and their influencing factors in the southwest mountainous region has important implications for the exploration of the evolutionary history and species conservation of the mountain flora.