We investigate how the effectiveness of green infrastructure (GI) to mitigate the frequency and magnitude of significant discharge events and combined sewer overflows (CSOs) depend on both climate and sewershed characteristics and propose a theoretical framework for a holistic assessment of GI's efficacy. The framework is based on the comparison of three characteristic timescales that control the production of peak discharge: rainfall duration (t r ), travel time in the sewer network (t n ), and the duration of rain that would be required to fill the GI's storage (t GI ). Storm events can then be characterized by two ratios of these timescales: T n = t n /t GI and T r = t r /t GI . A third dimensionless number characterizes critical storms during which adverse events (such as CSOs) occur and allows us to identify the combinations of T n and T r for which GI may substantially mitigate those events. The results of numerical experiments with the model demonstrate that the storms for which GI can substantially reduce peak discharge and CSO volume typically occur in a narrow band of T n and T r . Within that band, the efficacy of GI may depend on the location of GI within the sewershed if network routing substantially affects the timing and magnitude of flood peaks. The proposed framework is applied to examine the efficacy of GI using historical precipitation data from two major U.S. cities: Philadelphia, PA, and Seattle, WA, and the results of this comparative analysis suggest that GI location is an important control on catchment-scale GI efficacy in Philadelphia, but less so in Seattle.Plain Language Summary Combined sewer overflows (CSO) occur when storm rainfall exceeds the capacity of the sewer system to drain it. Green infrastructure (GI) is intended to mitigate the occurrence and severity of CSOs. But how effective will it be in helping to manage CSOs? Here we present a theoretical framework to address this question, by focusing on the major physical controls on the efficacy of GI for managing CSOs, including the relative roles of climate, the size of the sewershed, and the location of the GI within it. The framework is based on three characteristic timescales: storm duration, travel time to the overflow location, and time required to fill GI storage. We use the framework to explore how GI might work differently in different places. The results show that GI is most effective under certain combinations of climate and sewershed conditions, and that the location of GI within the sewershed can be very critical. The latter effect was found to be more evident, for example, in Philadelphia, PA, than in Seattle, WA, due to differences in storm duration and intensity between these two places. In these ways, the proposed framework can support green infrastructure planning by providing insights on location-effectiveness tradeoffs.