To improve the performance of high specific speed centrifugal non-clogging submersible sewage pump, the 350QW 1500—16—90 sewage pump was designed by using unequal head hydraulic design method and traditional equal head hydraulic design method. Three different optimization plans were proposed and CFD software ANSYS CFX was applied to analyze the interior flow field of each plan under different conditions, the performance was predicted and the best plan was selected to test by internal flow characteristics and performance curves. It was demonstrated that using unequal head hydraulic design method can reduce the area of low pressure of impeller working face and backflow, central runner had the lowest relative velocity so that blade outlet of the pump had a uniform static pressure and velocity distribution. The predicted curve obtained by CFD technology and performance curves obtained by experiment of head and efficiency had the consistent variation. There was no saddle zone and overload phenomenon, which indicated that it satisfied the design requirements and the numerical simulation was accurate and it had guiding significance for the high specific speed sewage pump design. The absolute value of head curve slope increased with the increase of flow, the maximum efficiency point was occurred at 1699.93m3/h and maximum efficiency was 80.256%. Maximum efficiency point shifted to the large flow, where the efficiency curves changed gently, 0.9Q~1.3Q was high efficiency area which was conformed to be the operating characteristics of the sewage pump running at high flow conditions, it was helpful to improve the current situation of high energy consumption at sewage treatment for using unequal head hydraulic design method.