In this article, a mathematical fluid–structure–thermal model for fuel leakage of piston couples was developed, with consideration of the physical properties of fuel, elastic deformation, and temperature distribution along the seal length. The calculated results were compared with experimental static fuel leakage data. Based on this model, the effects of various factors on the fuel leakage were investigated. The results showed, at pressures under 100 MPa, the most dominant influence on the fuel leakage of a piston couple was the initial clearance; however, as the pressure increased from 100 to 200 MPa, the influence of the initial clearance gradually weakened, while the effects of the piston diameter, elastic modulus, and diameter of the piston sleeve increased and became more significant; in this case, the piston diameter replaced the initial clearance as the most dominant factor. At a pressure range of 200–300 MPa, the effects of the elastic modulus exceeded the effects of the initial clearance and became the second most important factor. Therefore, simply adjusting the initial clearance is not an effective method to reduce fuel leakage. An increase in the seal length significantly influences the fuel leakage only under relatively low-pressure conditions, as the effect weakens with increasing pressure. As a result, under high-pressure conditions, it is necessary to consider both the diameter of the piston and the elastic modulus to reduce the fuel leakage.