Full-open, straight-blade centrifugal pumps have the advantages of simple structure and high stability at high speeds. However, this type of centrifugal pump has a large internal energy loss and low efficiency. The flow loss caused by unstable flow accounts for most of the internal energy loss of a centrifugal pump, and this energy dissipates mainly to the surroundings of the pump in the form of pressure pulsation and vibration. In this study, to effectively understand the hydraulic behavior and energy loss in a centrifugal pump, the energy losses in the pump were numerically analyzed by the entropy generation method, the distribution of the energies of pressure pulsation and vibration was evaluated based on experimental results at different flowrates, and the correlation between flow and energy loss at 20% of the design flowrate (Qd) was investigated by high-order spectrum analysis. The energies of pressure pulsation and vibration in the experiment were evaluated by the root-mean-square (RMS) value. The distribution of the entropy generation rate (EGR) indicated large energy losses at the diffusion section of the volute, clearance, tongue, and blade inlet. At 20% of the design flowrate (Qd), the energy loss was caused by the backflow near the tongue, and the EGR at EP2 had a nonlinear fundamental characteristic frequency of 0.44fn. By bispectrum and coherence analysis, the nonlinear fundamental characteristic frequencies generated by the unforced flow were analyzed, and it was found that unforced flow was transmitted to one another in the near-tongue region.