Abstract: As the largest river-connected lake of the Yangtze River, Poyang Lake’s outflow channel serves as the sole passage for runoff and sediment from the five tributaries and adjacent areas into the Yangtze. Influenced by human activities, this channel has experienced significant scour over the past two decades, profoundly affecting the hydrodynamics of the lake in terms of receiving inflows from the five rivers and regulating outflows. Existing studies on channel scour have mostly focused on localized cross-sections. This study constructs a high-resolution two-dimensional hydrodynamic model based on measured cross-sectional and hydrological data to quantitatively analyze the impact of scour in the outflow channel of Poyang Lake on its hydrodynamics. Measured data indicate that from 2010 to 2020, the thalweg of the channel was scoured by an average of 1 m. By designing four scenarios in the model—original, weak scour (-0.5 m), moderate scour (-1 m), and strong scour (-2 m)—and comparing them with the original scenario, quantitative analysis reveals that: Spatially, the northern lake region (from Hukou to Duchang) responds most significantly to scour. Under the strong scour scenario in the dry season (January), the water level at Duchang Station decreases by 0.55 m, and the flow velocity in the channel section decreases by an average of 0.05 m/s. In contrast, the southern lake region (from Tangyin to Kangshan) shows a weak response, with an average water level decrease of 0.1 m and a flow velocity increase of 0.01 m/s. Temporally, the response of Poyang Lake to scour is most pronounced in the dry season (January), leading to a significant drop in water level and an increase in outflow. In the wet season (July), due to high incoming flow and water levels, the impact is negligible, with water level differences among scenarios less than 0.01 m. The outflow discharge at the Hukou section increases with the degree of channel scour, with a maximum increase of 190 m³/s and a maximum daily average discharge increase of 5.48%. The flood regulation capacity of Poyang Lake diminishes with increasing channel scour. Under the strong scour scenario, the 30-day flood storage volume decreases from 6.979 billion m³ to 6.931 billion m³, and the flood regulation ratio drops from 25.99% to 25.81%. The lake area shrinks as scour intensity increases, with a maximum reduction of 43.12 km² (-2.27%) during the rising water level period (March) under the strong scour scenario, while in the wet season (July), the reduction is only 6.37 km² (-0.21%). This study highlights that the hydrodynamic impacts of scour in the outflow channel of Poyang Lake exhibit spatial heterogeneity (stronger in the north, weaker in the south) and seasonal heterogeneity (stronger in dry seasons, weaker in wet seasons), providing a scientific basis for flood and drought regulation and the construction of hydraulic projects in Poyang Lake.