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Wastewater treatment plant (WWTP) discharge is often considered a principal source of surface water contamination. In this study, a three-dimensional fully-integrated groundwater–surface water model was used to simulate the transport characteristics and cumulative loading of an artificial sweetener (acesulfame) and fecal indicator bacteria (Escherichia coli) from WWTPs within a 6800 km2 mixed-use, highly impacted watershed in Ontario, Canada. The model, which employed 3.5 × 106 computational nodes and 15 layers, facilitated a comprehensive assessment of groundwater–surface water interactions under high and low flow conditions; processes typically not accounted for in WWTP cumulative effects models. Simulations demonstrate that the model had significant capacity in reproducing the average and transient multi-year groundwater and surface water flow conditions in the watershed. As a proxy human-specific conservative tracer, acesulfame was useful for model validation and to help inform the representation of watershed-scale transport processes. Using a uniform WWTP acesulfame loading rate of 7.14 mg person−1 day−1, the general spatial trends and magnitudes of the acesulfame concentration profile along the main river reach within the watershed were reproduced; however, model performance was improved by tuning individual WWTP loading rates. Although instream dilution and groundwater–surface water interactions were strongly dependent on flow conditions, the main reach primarily consisted of groundwater discharge zones. For this reason, hydrodynamic dispersion in the hyporheic zone is shown as the predominant mechanism driving acesulfame into near-stream shallow groundwater, while under high flow conditions, the simulations demonstrate the potential for advective flushing of the shallow groundwater. Regarding the cumulative impact of the WWTPs on E. coli concentrations in the surface flow system, simulated transient E. coli levels downstream of WWTPs in the watershed were significantly lower than observed values, thus highlighting the potential importance of other sources of E. coli in the watershed. Image 100146 • Integrated hydrologic models are effective for characterizing point source pollution impacts. • Acesulfame is an effective chemical tracer for validating watershed-scale models. • Groundwater – surface water interactions impart a dynamic influence on water quality. • With only point source WWTP emitters considered, instream FIB levels were underestimated. [ABSTRACT FROM AUTHOR]