It has been shown that climate change impacts the overall health of a river's ecosystem. Although predicting river health under climate change would be useful for stakeholders to adapt to the change and better conserve river health, little research on this topic exists. This paper presents a methodology predicting river health under different climate change scenarios. First, a multi-source, distributed, time-variant gain hydrological model (MS-DTVGM) was used to predict the runoff from a mountainous river in eastern China using the data from three existing IPCC5 climate change models (RCP2.6, RCP4.5, and RCP8.4). Next, a model was developed to predict the river's water quality under these scenarios. Finally, a multidimensional response model utilizing hydrology, water quality, and biology was used to predict the river's biological status and ascertain the impact of climate change on its overall health. The river is in a mountainous area near Jinan City, one of China's first “pilot” cities recognized as a “healthy water ecological community.” Our results predict that the overall health of the Yufu River, which is minimally influenced by human activities, will improve by 2030 due to the increased river flow due to an increase in rainfall frequency and subsequent peak runoff. However, the total nitrogen concentration is predicted to increase, which is a potential eutrophication risk. Therefore, effective control of nitrogen pollutants entering the river will be necessary. The increase in flow velocity (the annual average increase is ~0.5 m/s) is favorable for fish reproduction. Our methods and results will provide scientific guidance for policy makers and river managers and will help people to better understand how global climate change impacts river health. Display omitted •We presented a methodology for predicting future river health under climate change.•A remotely sensed hydrological model was used to predict future river runoff.•We set up a water quality model to predict future water quality status.•A multidimensional response model was adopted to predict future biological status.•This study can help make wise policies for adaptation to climate change.