The Three Gorges Reservoir (TGR) is one of the world's largest hydropower projects and plays an important role in water resources management in the Yangtze River. For the sake of disaster prevention and catchment management, it is crucial to understand the regulation capacity of the TGR on extreme hydrological events and its impact on flow regime in a changing climate. This study obtains historical inflows of the TGR from 1961 to 2019 and uses a distributed hydrological model to simulate the future inflows from 2021 to 2070. These data are adopted to drive a machine learning‐based TGR operation model to obtain the simulated outflow with TGR operation, which are then compared with the natural flow without TGR operation to assess the impact of TGR. The results indicate that the average flood peaks and total flooding days in the historical period could have been reduced by 29.2% and 53.4% with the operation of TGR. The relative declines in drought indicators including duration and intensity were generally less than 10%. Faced with more severe extreme hydrological events in the future, the TGR is still expected to alleviate floods and droughts, but cannot bring them down to historical levels. The impact of TGR operation on flow regime will also evolve in a changing climate, potentially altering the habitats of river ecosystems. This study proposes feasible methods for simulating the operation of large reservoirs and quantifying the impact on flow regime, and provides insights for integrated watershed management in the upper Yangtze River basin.