The goal of sustainable water quality management is to keep total pollutant discharges from exceeding the assimilation capacity of a water body. Climate change may influence streamflows, and further alter assimilation capacity and degrade river sustainability. The purposes of this study are to evaluate the effect of climate change on sustainable water quality management and design an early warning indicator to issue warnings on river sustainability. A systematic assessment procedure is proposed here, including a weather generation model, the streamflow component of GWLF, QUAL2E, and an optimization model. The Touchen creek in Taiwan is selected as the study area. Future climate scenarios derived from projections of four global climate models (GCMs) and two pollutant discharge scenarios, as usual and proportional to population, are considered in this study. The results indicate that streamflows may very likely increase in humid seasons and decrease in arid seasons, respectively. The reduction of streamflow in arid seasons may further degrade water quality and assimilation capacity. In order to provide warnings to trigger necessary adaptation strategies, an early warning indicator is designed and its 30-year moving average is calculated. Finally, environmental monitoring systems and methods to prioritize adaptation strategies are discussed for further studies in the future.