Long-term changes of 14 water constituents measured in continuously and water discharge proportionally collected samples of four Swiss rivers over a period of 39 years are analyzed using several statistical techniques. Possible drivers and causes for the identified trends and shifts are explained by consideration of catchment characteristics and anthropogenic activities. Water temperatures increased by 0.8–1.3 °C, whereas water discharges remained largely unchanged. Concentrations of alkalinity, total hardness, Ca, and Mg regulated by dominant carbonate lithologies in catchments increased by up to 10%. We attribute this change to an increase in the partial pressure of CO₂ in the subsurface, provoked by increasing temperatures. Re-oligotrophication processes in lakes also influence the behavior of alkalinity and silicic acid. In contrast to concentrations, most loads did not change significantly, due to their large variances. Therefore, no changes in overall weathering rates of carbonate rocks can be detected. The outgassing of CO₂ in rivers from the place of carbonate dissolution to measurement stations amounts up to 6% (mean) of CO₂ sequestered (mean 1.1 mol m⁻² a⁻¹) by the weathering of rock minerals. Changes in alkalinity/Ca/Mg ratios indicate an increase in calcite precipitation over time. Total nitrogen concentrations and loads peaked at the end of the 1980s and then decreased up to 50%, while NO₃ concentrations showed almost no changes. This dynamic matches the changes in the agricultural N balance. Concentrations and loads of Na and Cl increased up to 60% due to an increase in the various uses of rock salt.