To uncover climate–water quality relationships in large rivers on a global scale, the present study investigates the climate elasticity of river water quality (CEWQ) using long-term monthly records observed at 14 large rivers. Temperature and precipitation elasticities of 12 water quality parameters, highlighted by N- and P-nutrients, are assessed. General observations on elasticity values show the usefulness of this approach to describe the magnitude of stream water quality responses to climate change, which improves that of simple statistical correlation. Sensitivity type, intensity and variability rank of CEWQ are reported and specific characteristics and mechanism of elasticity of nutrient parameters are also revealed. Among them, the performance of ammonia, total phosphorus–air temperature models, and nitrite, orthophosphorus-precipitation models are the best. Spatial and temporal assessment shows that precipitation elasticity is more variable in space than temperature elasticity and that seasonal variation is more evident for precipitation elasticity than for temperature elasticity. Moreover, both anthropogenic activities and environmental factors are found to impact CEWQ for select variables. The major relationships that can be inferred include: (1) human population has a strong linear correlation with temperature elasticity of turbidity and total phosphorus; and (2) latitude has a strong linear correlation with precipitation elasticity of turbidity and N nutrients. As this work improves our understanding of the relation between climate factors and surface water quality, it is potentially helpful for investigating the effect of climate change on water quality in large rivers, such as on the long-term change of nutrient concentrations.