Green infrastructure (GI) is a contemporary approach to the management of stormwater and limits its intrusion into wastewater collection systems. GI practices, such as bioretention systems, affect the local water cycle by encouraging detention, infiltration, and evapotranspiration of intercepted runoff. They may also affect water quality by either contributing nutrients to stormwater or removing pollutants through filtration or biogeochemical transformation. Therefore, for a complete understanding of GI effects, a thorough water-cycle monitoring and simulation approach is needed. In this study, the Green Infrastructure Flexible Model (GIFMod) was used to simulate hydraulic and water quality processes in a system of two bioretention cells, built in series, that drain a small catchment (3.41 ac). The goal was to evaluate the long-term effectiveness of the system at reducing hydrologic and nutrient loads to a combined sewer system. The calibrated model was used to determine cumulative load reductions afforded by the GI system over a 3-year simulation and to evaluate different design scenarios on the performance of the bioretention systems. The results show that hydraulic retention time (HRT) mainly regulates the effectiveness of the bioretention system for flow reduction. The bioretention systems at their current design reduced approximately 50% of the runoff volume before discharging into the sewer system. The engineered soil of the bioretention was found to be a net source of nitrate in the effluent. The results of the multiple design scenarios indicated that adding a riser-type outlet and increasing the storage volume of the aggregate layer of the bioretention system would result in moderate improvements in reduction efficiency, while increasing the catchment area would significantly reduce its effectiveness. Of these modifications, adding a riser feature constitutes a cost-effective design feature that in this case was easily implemented post construction and, therefore, is recommended for similar bioretention installations.