The ultra-low specific speed centrifugal pump has been widely applied in aerospace engineering, metallurgy, and other industrial fields. However, its hydraulic design lacks specialized theory and method. Moreover, the impeller and volute are designed separately without considering their coupling effect. Therefore, the optimal design is proposed in this study based on the local entropy production theory. Four geometrical parameters are selected to establish orthogonal design schemes including blade outlet setting angle, wrapping angle volute inlet width, and throat area. Subsequently, a 3D steady flow with Reynolds stress turbulent model and energy equation model is numerically conducted and the entropy production is calculated by a user-defined function code. The range analysis is made to identify the optimal scheme indicating that the combination of local entropy production and orthogonal design is feasible on pump optimization. The optimal pump is visibly improved with an increase of 1.08% in efficiency. Entropy production is decreased by 16.75% and 6.03% in impeller and volute, respectively. High energy loss areas are captured and explained in terms of helical vortex and wall friction, and the turbulent and wall entropy production are respectively reduced by 3.82% and 14.34% for the total pump.