High nutrient discharge from groundwater (GW) into surface water (SW) have multiple undesirable effects on river water quality. With the aim to estimate the impact of anthropic pressures and river–aquifer interactions on nitrate status in SW, this study integrates two hydrological simulation and water quality models. PATRICAL models SW–GW interactions and RREA models streamflow changes due to human activity. The models were applied to the Júcar River Basin District (RBD), where 33% of the aquifers have a concentration above 50 mg NO3−/L. As a result, there is a direct linear correlation between the nitrate concentration in rivers and aquifers (Júcar r2 = 0.9, and Turia r2 = 0.8), since in these Mediterranean basins, the main amount of river flows comes from groundwater discharge. The concentration of nitrates in rivers and GW tends to increase downstream of the district, where artificial surfaces and agriculture are concentrated. The total NO3− load to Júcar RBD rivers was estimated at 10,202 tN/year (239 kg/km2/year), from which 99% is generated by diffuse pollution, and 3378 tN/year (79 kg/km2/year) is discharged into the Mediterranean Sea. Changes in nitrate concentration in the RBD rivers are strongly related to the source of irrigation water, river–aquifer interactions, and flow regulation. The models used in this paper allow the identification of pollution sources, the forecasting of nitrate concentration in surface and groundwater, and the evaluation of the efficiency of measures to prevent water degradation, among other applications.