Mixed-flow pump is one of the most broadly applied sorts of power equipment in the field of petrochemical and water conservancy. The effects of inlet pre-rotation on the energy characteristics and operational stability of a pump is a significant consideration. The aim of this study is to analyze the relationship between inlet pre-rotation and the total energy consumption of a mixed flow pump by developing a predictive model. The impact of pre-rotation on the pumping performance and energy conversion for a typical mixed-flow pump has been investigated by a combined approach of theoretical derivation, numerical simulation and experimental verification. Validation of the numerical methods was achieved by comparing the results to the experimentally obtained data. A prediction model was developed for head and power, which incorporated inlet pre-rotation. Moreover, the effects of pre-rotation on the flow structure of the mixed-flow pump was analyzed. It was found that pre-rotation led to an increase in the incoming flow angle, resulting in unstable flow patterns causing secondary flows and low-pressure vortex in the impeller flow path. This induced a rise in energy consumption of the impeller. The prediction model and analysis of the internal flow structure provide a theoretical foundation for predicting the hydraulic performances of mixed-flow pumps under pre-rotation conditions and improving their stability of operation.