Water quality assurance is the primary factor for the successful operation of water diversion projects across river basins. The rapid prediction of water pollution is the basis for timely and effective emergency control and disposal measures. In China, since the open channels intersect with numerous waterways and traffic arteries, water transfer projects are prone to sudden water pollution accidents. In this paper, the rapid prediction method was developed for sudden water pollution accidents that possibly occurred in the East Route of the South-to-North Water Diversion Project (ERP) in Shandong Province. With the empirical formula of the pollution transfer law, a rapid prediction model of water quality (WQRP) was established based on the simulation of the typical accidents in the main channel. Finally, four typical accidents were selected as application examples, and the prediction results were compared with the results from a computer numerical simulation to demonstrate the validity of the model. The results showed that the prediction results by the WQRP model meet the accuracy requirements. This method is of great significance for providing water transport security in the extreme conditions of long-distance water transfer projects.