This study investigates 72 catchments across the federal state of Baden‐Wuerttemberg, Germany, for changes in water quality during low‐flow events. Data from the state's water quality monitoring network provided seven water quality parameters (water temperature, electrical conductivity, concentrations of chloride, sodium, sulfate, nitrate, and phosphate), which were statistically related to streamflow variability. Water temperature changes during low‐flow showed seasonal dependence. Nitrate concentrations revealed high spatial heterogeneity with about one third of the stations showing decreasing values during low discharge. For most other parameters, concentrations increased during low‐flow. Despite consistent trend directions, the magnitudes of changes with streamflow differed markedly across the state. Both multiple linear regression and a multiple analysis of variances were applied to explain these differences with the help of catchment characteristics. Results indicated that for sulfate and conductivity, geology of the catchments was the most important control, whereas for chloride, sodium, and nitrate, sewage treatment plants had the largest influence. For phosphate, no clear control could be identified. Independent from the applied method, land use was a less important control on river water quality during low‐flow than geology or inflow from sewage treatment plants. These results show that the effects of diffuse and point sources, as well as those of natural and anthropogenic sources differ for different water quality parameters. Overall, a high diversity of potential water quality deterioration signals needs to be considered when the ecological status of rivers is to be protected during low‐flow events.