Past years have witnessed the transformation of land use at a high frequency and a warmer and drier climate in the Eastern Tibetan Plateau region. To fully understand the spatial-temporal variation of ecosystem services against the changing global backdrop and to provide scientific ecosystem management measures for decision-making, a study was conducted to investigate the major ecosystem services: water yield, soil conservation and crop production from 1990 to 2015 in the Eastern Tibetan Plateau region. Three scenarios—climate change only, land use change only and both land use and climate change—were included in this study to analyze the response of ES to the above-mentioned global changes. The results show that (1) the total quantity of ES reduced in all the three scenarios, the annual ES change was scenarioII < scenarioIII < scenarioI and the periodical characteristics are present in this region; (2) the ES change in spatial distribution varied with different climate change patterns and land use transfer directions; (3) the ES composition of each ecosystem varied with different driving scenarios and different responses of the forest and wetland on climate change and land use changes were observed. Moreover, the trade-off under land use change and climate change respectively was observed in this study. Based on the results, we recommend that the local government take this trade-off and climate change into account when making decisions, continue with desertification control and improve the quality of grassland as well as forests—these efforts should enable us to achieve sustainable development of human beings and the natural ecosystem.