Pumps are a type of general machine with many varieties and extensive application. To simulate really the self-priming process of multistage self-priming centrifugal pump, the numerical calculation of gas-water two-phase flow on a four-stage self-priming pump was performed based on ANSYS CFX software. Moreover, a transparent plastic tube was installed at the pump outlet, and the photographic technology was used to observe the appearance of gas-water escape during the self-priming process of multistage self-priming centrifugal pump. The experimental results were compared with the numerical results. It is found that the whole self-priming process of self-priming pump can be divided into three stages: the initial self-priming stage, the middle self-priming stage, and the final self-priming stage. Moreover, the self-priming time of the initial and final self-priming stages accounts for a small percentage of the whole self-priming process, while the middle self-priming stage is the main stage in the self-priming process, which determines the length of self-priming time. The experimental results are very close to the numerical results in the initial and middle self-priming stages.