This research is used to study the quality of water of the Kufa River, a branch of the Euphrates River, which flows through the Najaf city in Iraq. The Kufa River receives several point sources of pollution along the river. In order to protect the river from the pollution that leads to destroying the environment of the river, it is necessary to model the quality of the Kufa River’s water for studying the variations of the water quality parameters and understanding the transport of pollution within the river. The created model is used to manage the flow operation in minimum and maximum conditions, especially for the current time, with the decline in the water resources. To develop the water quality model, MIKE 11 was used to simulate the water quality parameters such as Biochemical Oxygen Demand (BOD), Dissolved Oxygen (DO), Total Dissolved Solids (TDS), and Phosphate (PO4). The developed model was calibrated for 2023 and validated for 2024, using observed water levels and measured water quality collected for this study. The developed hydrodynamic and water-quality model shows a good match between observed and simulated water-quality parameters, with a correlation coefficient exceeding 80%. Using the calibrated model, three proposed scenarios were introduced to study the flow operation and manage the Kufa River. The two-way ANOVA results indicate a significant difference among the flow operation scenarios and the t-test results show a significant difference between the sites in the scenarios, especially for TDS and PO4.