Abstract: This study aims to analyze the impacts of Three Gorges Reservoir (TGR) operation on the regional water balance in the downstream area and provide a basis for adaptive regulation that coordinates engineering scheduling with regional demands. To address the data linkage challenge in accounting for socio-economic water use (agricultural, domestic, industrial) and natural system components (precipitation, evaporation, and runoff), we integrated meteorological/hydrological observations, water resources bulletins, and multi-source data products, deriving water balance indices that account for both component via spatiotemporal interpolation. The results show that before the reservoir construction, the water balance indices exhibited a non-significant decline, but increased significantly afterward, accompanied by a decrease in the mean intra-annual concentration index, reflecting the impact of the TGR’s scheduling of decreasing flood discharge and increasing low flow. A three-level regulation scheme was proposed based on index thresholds: medium and low-flow schemes better align with the synergized objectives of flood control and water supply, whereas high-flow schemes prioritize ecological baseflow at the cost of potential trade-offs in stored energy loss. The proposed scheme considers the interaction mechanism between hydraulic engineering operation and the regional water resources system, offering a scientific reference for optimizing reservoir operation strategies and coordinating regional development demands.