Climate change and extreme weather events (such as droughts, heatwaves, rainstorms and floods) pose serious challenges for water management, in terms of both water resources availability and water quality. However, the responses and mechanisms of river water quality under more frequent and intense hydroclimatic extremes are not well understood. In this Review, we assess the impacts of hydroclimatic extremes and multidecadal climate change on a wide range of water quality constituents to identify the key responses and driving mechanisms. Comparison of 965 case studies indicates that river water quality generally deteriorates under droughts and heatwaves (68% of compiled cases), rainstorms and floods (51%) and under long-term climate change (56%). Also improvements or mixed responses are reported owing to counteracting mechanisms, for example, increased pollutant mobilization versus dilution during flood events. River water quality responses under multidecadal climate change are driven by hydrological alterations, rises in water and soil temperatures and interactions among hydroclimatic, land use and human drivers. These complex interactions synergistically influence the sources, transport and transformation of all water quality constituents. Future research must target tools, techniques and models that support the design of robust water quality management strategies, in a world that is facing more frequent and severe hydroclimatic extremes.