Hydraulic water plunger pumps have come to be widely used in coal mining, seawater desalination, and oil exploitation due to their high output pressure and large flow characteristics. In a high-pressure large-flow plunger pump, the leakage of the annular channel of the plunger pair is an essential factor affecting volume efficiency. The axial pressure gradient exists in the fluid inside the annular channel, resulting in the plunger and plunger sleeve forming similar funnel-like shapes. Moreover, the characteristics of large diameter, high working pressure, and low fluid viscosity of the plunger pump will lead to the complicated flow of the annular channel. The influence of eccentricity and structural deformation on leakage is difficult to evaluate. Therefore, considering the deformation gradient and eccentricity of the plunger pair and the compressibility of the water, the deformation equations and leakage equations of the annular channel under the laminar and turbulent flow state are derived in this study. The eccentricity and leakage of the annular channel under different pressure conditions are measured using a built sealing test bench. It is proved that the discrepancy between the calculated model and the experimental results is less than 6% under different pressures, which effectively predicts the sealing performance of plunger pumps. The results show that under the laminar flow condition, the effects of eccentricity, structural deformation, and medium compressibility on leakage are 148%, 4.92%, and 0.92%, respectively. In turbulent conditions, they were 31%, 2.84%, and 1.19%, respectively. Besides, the reasonable material pairing of the plunger friction pair can reduce the variation of leakage due to structural deformation.