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Water changing conditions of a lake will affect the physical and hydrological conditions and ecology of the lake and groundwater. The unique "river-lake phase" transition of the Poyang Lake complicates the surface water-groundwater exchange process in the area. Therefore, this study uses Visual MODFLOW to build a 3D numerical model of groundwater transient flow and uses the LAK3 module to realize the dynamic simulation of the lake water area by inputting the runoff from five rivers into the lake and the Poyang Lake into the Yangtze River. The RMSE between the simulated and measured values of lake water level is 0.225 m, and between the simulated and measured values of groundwater level is 0.571 m. The month-on-month ratio variation of the Poyang Lake area simulated by the model ranges from −41% to 83%, consistent with the remote sensing images. This model reduces the constraint of lakes as boundary conditions, can effectively depict the frequently-changing water level and lake area, and accurately simulate the response of groundwater flow field and surface water-groundwater interaction relationship to the height dynamics of lake water. During the dry season, the lake is mainly recharged by groundwater, with an exchange flux ranging from 2.03×107 to 10.58×107 m3/mon. During the wet season, the lake water discharges into groundwater with an exchange flux ranging from 2.04×107 to 16.53×107 m3/mon, with the average groundwater level rise in the lake region and surrounding areas by 2~3 m compared to the dry season. The groundwater flows from the lake region to the surrounding areas. This study contributes an effective numerical simulation method for areas with dramatic changes in surface water bodies. The results can provide a basis for future water resources management and environmental assessment in the Poyang Lake Plain.