The Nhue–Day river basin is well–known by its critical water quality, causing negative impacts on locals’ health as well as landscape and environmental storage in recent years. The study develops artificial intelligence (AI) model to simulate the water quality of Nhue–Day river, based on the results of hydrodynamic simulation and water quality in the hydraulic model MIKE11. The input data include: topography, hydrological, and discharge data at monitoring locations to simulate river water quality. The AI model with MLP – ANN algorithm builds a regression relationship between river water flow and concentration of discharge sources (predictor variables) with water quality indicators (dependent variable) to forecast river water quality at control locations under different control and waste management scenarios quickly. The results from the AI model are close to the results from the MIKE 11 model with an R2 index of 0.98 or higher, with simulation time being thousands of times faster than hydraulic model, which is an effective tool, allowing to get water quality forecast quickly. This study provides management tools for managers to quickly assess the impact of solutions to planning, managing, and controlling water pollution in the Nhue – Day river basin.