Leaching of nitrate from agricultural land to groundwater and the resulting nitrate pollution are a major environmental problem worldwide. Its impact is often mitigated in aquifers hosting sufficiently reactive reductants that can promote autotrophic denitrification. In the case of pyrite acting as reductant, however, denitrification is associated with the release of sulfate and often also with the mobilization of trace metals (e.g., arsenic). In this study, reactive transport modeling was used to reconstruct, quantify and analyze the dynamics of the dominant biogeochemical processes in a nitrate-polluted pyrite-containing aquifer and its evolution over the last 50 years in response to changing agricultural practices. Model simulations were constrained by measured concentration depth profiles. Measured 3H/3He profiles were used to support the calibration of flow and conservative transport processes, while the comparison of simulated and measured sulfur isotope signatures acted as additional calibration constraint for the reactive processes affecting sulfur cycling. The model illustrates that denitrification largely prevented an elevated discharge of nitrate to surface waters, while sulfate discharges were significantly increased, peaking around 15 years after the maximum nitrogen inputs.