To improve water quality and alleviate pollution in Changshou-Fuling section of the Three Gorges Reservoir Area, an analysis methodology of regional key discharge outlet based on hydrodynamic-water quality model was developed. The EFDC model was used to study the impact of different discharge outlets on the transport of contamination in the study area by using the concept of pollutant mixing zone and pollutant mixing zone per unit load. Model calibration was conducted using observed data in 2008. Results indicated that EFDC could perfectly simulate hydrodynamics characteristics and contaminant transport process. Calculated results of pollutant mixing zone per unit load showed that the discharge outlet location in Fuling is more reasonable than that in Changshou. This study provides useful information for optimization of discharge outlets location and prediction of pollutant mixing zone in the study area, which is important for the government to make water pollution control measures.