Water quality safety is of critical importance in environmental improvement, particularly with respect to drinking water resources worldwide. As the main drinking water sources in Shenzhen, China, the cascade reservoirs comprising the Shiyan, Tiegang, and Xili Reservoirs are highly regulated and have experienced water quality deterioration in recent years. In this study, a three-dimensional hydrodynamic and water quality model was established using the Environmental Fluid Dynamics Code (EFDC) for the cascade reservoirs. The relationships between water quality and improvement measures were quantified and the main pollution sources for individual reservoirs were identified. Results showed that the hydrodynamic and water quality model well captured the spatial and temporal variations of water level, the permanganate concentration index (COD Mn ), and total nitrogen (TN), with high resolution in the cascade reservoirs. The correlation coefficients between simulations and observations were close to 1.00 for water levels, and over 0.50 for COD Mn and TN concentrations. The most effective methods for water quality improvement were the reduction of the runoff load for TN and transferred water load for COD Mn in the Shiyan Reservoir, reduction of the transferred water load in the Tiegang Reservoir, and an increase in transfer water volume, especially in the flood season, in the Xili Reservoir. Internal pollution sources also played an important role in water pollution, and thus sedimentation should be cleaned up regularly. This study is expected to provide scientific support for drinking water source protection and promote the application of hydrodynamic model in water quality management.