An improved understanding of the three-dimensional structure of wind-driven currents under different wind speed, wind direction and water levels is highly valuable for lake pollution control, ecosystem restoration as well as resources utilization. In this study, a three-dimensional hydrodynamic model was setup and validated using observed current profiler data for Lake Hongze. Typical features of wind speed and wind direction were determined using 46-yr wind observational data. The spatial structure of lake current was simulated under 16 wind directions, 13 wind speeds and 20 water levels. Results suggest that the hydrodynamic model generally captured the dynamics of three-dimensional current structure in Lake Hongze. Wind-driven currents exhibit considerable difference with the switch of wind direction. Current velocity increases rapidly with the raising of wind speed, and the surface layer is much more pronounced than other four vertical layers. The vertical-averaged current velocity in the lake basins of Lihewa, Chengzihu and Southern Basin exhibit a unimodal pattern with the raises of water level, with velocities peak at water levels of 12.7 m, 12.4 m and 12.2 m for the three basins, respectively.