To explore the impact of expanding Nanyang Sewage Purification Center (NSPC) on the main sewage discharge area of Bai River, we constructed a 2D hydrodynamic-water quality model based on surface water modeling system (SMS) and Mike21. Simulating three sewage discharge conditions in wet, normal, and dry season, we evaluated three indicators (COD, NH3-N, and BOD5) by the single-factor pollution index and provided recommendations for water environment management. The results showed that, maximum absolute error of water level was 0.08 m, percentage bias coefficient of COD, NH3-N and BOD5 were 19.3%, 16.2% and 23.1%, indicating the SMS and Mike21 coupling model was applicable; water quality of the assessment section were upgraded from the original class IV, V, V (Condition 1) to class IV, III, II (Condition 2) and class IV, III, III (Condition 3) in the wet, normal and dry season, indicating that NSPC's expansion had improved the water quality of the assessment section; as the primary pollutant, BOD5 concentration in the downstream was lower than the upstream, which was due to the dilution effect of river. Therefore, on the basis of expanding NSPC, we recommend to remediation of BOD5 by physical, chemical, and biological methods. This study broadens new ideas for the application of Mike21, and provide a reference for the prevention and improvement of river water pollution in urban areas.