ABSTRACT Identifying runoff changes and quantifying the impacts of climate change and human activities are important for water resources planning and management in river basins. The impacts of climate change and human activities on runoff can be more accurately assessed through scientific hydrological modeling and data analysis methods. In this study, an integrated assessment framework was established to quantitatively separate the driving mechanisms of runoff at different time scales. The results show that the runoff of Wu River has shown a decreasing trend since 2004, with a change degree of 56%, and the monthly average flow indexes of August and September have changed significantly, both are over 90%. The NSE coefficient of the SWAT simulation effect is above 0.8, we validate the simulation results based on the LSTM model. It was found that climate change was the main factor affecting the runoff of Wu River, with the contribution rates reaching 60 and 57%, respectively. Pearson correlation analysis found that rainfall was the most important factor affecting the runoff. The results of this study are helpful to formulate effective water resources management policies and measures to ensure the sustainable utilization and management of water resources in the Wu River Basin.