Pump station engineering is a water conservancy project that utilizes water pump units for energy transfer and conversion, and safe water transportation. This study ensures the safe and efficient operation of the pumping station system by taking a pump station project containing seven water pump units as the research object. Under the premise that the total water intake of the pumping station is certain, the flow distribution of the pumping station is optimized with the working flow and head as the constraint function, and the minimum operating cost as the objective function, and the required number of operating units is determined to obtain the optimal combination of flow distribution and the corresponding working flow of each operating unit. Compared with previous studies, the novel feature of this study is that a genetic algorithm is used to optimize the power-up combination and rationally distribute the flow, which can minimize the energy consumption and maximize the operation efficiency of the pumping station. Then, a genetic-algorithm-based optimization method is constructed for unit operation combination and flow distribution. The optimized combination of units is evaluated by using the uniformity of flow velocity at the inlet section of the water pump and the average deviation angle of the section as indicators. The results indicate that, when each operating unit in the pump station has the same working flow distribution, the total input power of the pump station is at maximum. As the differences increase in the working flow rates allocated to each operating unit, the total input power of the pump station decreases. Through the proposed schemes, the optimal operating combination and flow distribution of the pump station system can be achieved when the total water intake is constant, thereby enabling efficient operations and creating maximum economic and social benefits.