Human activities and environmental change can impact the supply of ecosystem services (ESs) as pressures. Understanding the mechanisms of these impacts is crucial to support ecological conservation and restoration policy and applications. In this study, we highlighted the contribution of vegetation to mitigating these impacts on ESs in the Qinghai-Tibet Plateau (QTP) of China. First, we identified hot and cold spots of pressures from human activities and environmental factors and mapped the cumulative provision of five ESs (i.e., water yield, soil retention, carbon sequestration, habitat quality, and landscape aesthetics). Then, we clustered these ESs into five bundles based on their supply level. Furthermore, structural equation modeling was used to quantify the pathways of multiple pressures on ESs. The results indicated that 1) for 2000, 2010 and 2019, the percentages of hot spots with high pressure were 28.88%, 27.59% and 45.66% respectively, with significant spatial heterogeneity from northwest to southeast; 2) both regions with high and low cumulative ES values experienced increased volatility; and 3) the joint effects of multiple pressures shaped ESs through pressure-ES (direct) and pressure-vegetation-ES (indirect) pathways. Specifically, precipitation had the largest positive effect on regulating services (rα ≥ 0.76), and landscape fragmentation had the largest negative effect on cultural services (-0.10 ≤ rα ≤ -0.07). Vegetation played an important role in modulating multiple pressures on ESs. This study contributes to ecosystem management by effectively coping with anthropogenic and environmental pressures and sustaining the supply of ESs, particularly in alpine and plateau regions. Copyright © 2023 Liu, Lü, Zhao and Fu.