Sewer interception systems have been built along rivers in rapidly urbanizing areas to collect unregulated sewage discharges due to misconnections between storm sewers and sanitary sewers. During storm events, combined sewage might overflow from these systems into rivers through orifices and deteriorate water quality in rivers. Interception system overflows (ISOs) from different orifices in a sewer interception system might interact with each other, therefore pollutants from ISOs show a spatial variation. This paper aims to understand the spatial variation of pollutants from ISOs for informed decision making. In this study, an urbanized catchment in China is chosen as the study area, and the Storm Water Management Model (SWMM) is used to examine the spatial variation of pollutants from ISOs and to analyze the effect of sewer separation on ISOs. The results obtained from the case study indicate that: (1) Critical rainfall amounts which trigger overflows decrease downstream in an interception system while annual ISO volumes and pollutant loads from ISOs increase downstream; additionally, these variations are influenced by sizes and slopes of interceptors; (2) Runoff is the main source of COD from ISOs while sewage is the main source of NH₃-N, and ratios of pollutants from sewage to ISOs increase downstream; (3) Sewer separation can significantly reduce pollutant loads from sewage to ISOs, but it cannot significantly reduce pollutant loads from runoff. In order to mitigate ISO pollution, it is suggested to increase conveyance capacities of interceptors in the downstream, separate sewage from runoff, and promote source control for urban runoff in highly urbanized areas.