Climate change and other disturbances significantly impact hydrogeochemical exports from mountainous headwater catchments such as the Upper Colorado River Basin. Developing a mechanistic understanding of how the physical and chemical processes interact in time and space in an integrated manner is key to quantifying the future impacts of such disturbances. The hydrogeochemical response of a mountainous catchment in the 2010–2019 period is evaluated quantitatively using a high-resolution model that simulates integrated hydrology, and transport and reactions for selected solutes and minerals. The model assumes that pyrite is present only at depth while calcite is distributed uniformly, and captures the observed C-Q reasonably well. Distinct C-Q dynamics are observed in an average (WY16), a wet (WY17), and a dry (WY18) water year. The model also quantifies the water fraction from surface, shallow and deep groundwater compartments using tracers, and suggests greater groundwater contributions to peak stream discharge in the dry WY18. Results demonstrate that calcium concentrations do not change significantly from year to year, while sulfate shows significant temporal variability. Pyrite dissolution is affected by the changing hydrological drivers where it is enhanced in the dry WY18; calcite dissolution supplements calcium dilution under high flow conditions. The model simulates the reaction hotspots controlled by hydrological conditions, and the spatially-resolved results show that higher soil saturation and less snowpack occur earlier on the south-facing side than on the north-facing side. This is a first-of-its-kind demonstration of a model that integrates hydrologic processes, including evapotranspiration, and reactive transport to enable a predictive understanding of hydrogeochemical exports