Green infrastructure (GI) has gained traction as a preferred stormwater management practice for its benefits in mimicking pre-development hydrology, removing non-point source pollution, and improving water quality. However, trends in land development and climate variability can mask the system-wide benefit of GI and increase the difficulty of detecting and evaluating the integrated, watershed-scale hydrologic impact of GI. There is a strong and urgent need to quantify the system-scale impact of existing and future GI implementations and prioritize GI investments. In this study, using Milwaukee, WI as a case study, we obtained estimations of future climates by integrating the downscaled Global Climate Model (GCM) outputs with historical ground precipitation observations. Statistical downscaling was performed on 28 CMIP6 ensemble members and 3 Shared Socio-economic Pathways (SSP2-4.5, SSP3-7.0, and SSP5-8.5) at mid-century and end-of-century. With a system-scale validated urban hydrologic model (SWMM), we evaluated the sewer collection system’s response to spatially varied storm forcings through both event-based and continuous simulations. A range of performance metrics for quantifying collection system impact to treated flows, sanitary and combined sewer overflows, and tunnel were defined, and compared across GI scenarios. The results from event-based, spatially focused GI screening runs were used to identify system-scale GI scenarios, which were further evaluated through both event-based and continuous simulations. The results of this study will provide a thorough assessment about the system-scale impact of GI, priority locations for GI, and the robustness of GI hydrologic and hydraulic benefits across potential climate futures.