The risk of flood or waterlogging in irrigation districts has increased due to global climate change and intensive human activities. A Model of Optimal Operation of Drainage Works (MOODW) for flat irrigation district was established by incorporating the hydrological model of waterlogging process and waterlogging loss estimation, which was solved by an optimization method of genetic algorithm. The model of waterlogging process was built based on a modified Tank model and hydrodynamic model for the ditch-river system. The waterlogging loss is calculated under the condition of inconstant inundated depth by linear interpolation. The adaptive genetic algorithm with the global optimization function was selected to solve the model. With an extreme rainfall events in Gaoyou irrigation district as cases, results showed that operation time and numbers of pumps increased; thus, operating costs were 1.4 times higher than before, but the yield loss of rice decreased by 35.4% observably. Finally, the total waterlogging loss was reduced by 33.8% compared with the traditional operation of waterlogging work. The most significant improvement was found in units with high waterlogging vulnerability. The MOODW can provide the waterlogging information visually and assist the district manager in making a reasonable decision.