The purpose of this study is to disclose the water resource risks influenced by climate extremes and human activities and therefore to propose a management strategy for the river basins (Lancang and Jinsha rivers) in the Hengduan Mountains, Southwest China. In this study, a slope changing ratio of cumulative quantity (SCRCQ) approach is introduced to separate the contributions of climate change and human activities from runoff changes, and to propose a conceptualmodel to secure a management strategy under the implications of the changing environment, based on these datasets, including observation climate and runoff data, satellite remote sensing images (MODIS and Landsat) and the observed land use data. Through this investigation, the following results were achieved. Firstly, the annual average runoff exhibited a non-significant decreasing trend fromupstream to downstreamover the Lancang and Jinsha riverswith a change rate of −26.3mm/10 year, the runoff had a sharp decrease in drought years, especially in 1984, 2006 and 2009 by 26%, 28%and 24%, respectively, at the Jiajiu station. Secondly, the cropland decreased by 803 Km2 and the forestland increased by 423 Km2 which finally resulted in a significant decline in runoff, the change rate was −15mmper year (4%) and −71 mmper year (8%) over the Lancang and Jinsha river basins, respectively from 2000 to 2010. Thirdly, the average observed runoff in the “pre-dam” period (1980–1992) increased by 7% in the “post-dam” period (1993–2015). Improving the weather modifications and water-saving technology can help retain water resources in the rainy seasons to relieve drought in the dry seasons. Finally, a comprehensive assessment model was applied to select plant species in the ecological restoration areas,which have implications for environmental protection, water resourcemanagement and ecological restoration in the rivers of southwest China.