With the interaction of global change and human activities, the contradistinction between supply and demand of ecosystem services in the Qinghai-Tibet Plateau is becoming increasingly tense, which will have a profound impact on the ecological security of China and even Asia. Based on land cover data on the Qinghai-Tibet Plateau in 1990, 2005, and 2015, this paper estimated the supply capacity of ecosystem services using the value equivalent method, calculated the demand for ecosystem services using population density and economic density, established an ecosystem risk index based on the idea of an ecosystem service matrix to reveal the spatio-temporal pattern of the supply and demand of ecosystem services in the Qinghai-Tibet Plateau, and identified the potential ecological risk areas arising from the imbalance between supply and demand. The results showed that: (1) In terms of the spatio-temporal pattern of land use change, the desert area of the Qinghai-Tibet Plateau decreased the most with 26,238.9 km², and other types of land use increased, of which construction land increased by 131.7%; (2) In terms of the supply and demand of ecosystem services, the Qinghai-Tibet Plateau was mainly dominated by low-level surplus areas, accounting for 64.0%, and the deficit in some areas has worsened significantly; and (3) In terms of division pattern of ecological risk areas, the Qinghai-Tibet Plateau presented characteristics of high risk in the east and low risk in the west. The high-risk area accounted for 1.1%, mainly distributed in the Huangshui Valley and the “One River and Two Tributaries” (Yarlung Zangbo River, Lhasa River, Nianchu River). The research results can provide reference for ecosystem management and policy formulation of the Qinghai-Tibet Plateau and have important significance for realizing the coupling and coordinated development of human–land relationship in Qinghai-Tibet Plateau.