In service, thermal-mechanical coupling conditions can exacerbate stress relaxation of O-rings and lead to their thermal expansion, further complicating the sealing problem. A finite element method is developed to simulate the mechanical deformation behavior of O-rings under thermal-mechanical coupling conditions, and its validity is verified by comparison with experimental data. Based on a substantial amount of simulation data, it is found that a dimensionless contact stress can be used as an indicator of the degradation of sealing performance and can be related to temperature T and time τ in the form of an aging kinetic equation. By combining this equation with the existing interfacial leakage model, an approach of predicting the long-term leakage rate of O-rings is proposed to quantitatively evaluate the effect of various factors on the performance of O-rings, and some important conclusions are drawn. Regarding the effect of temperature on O-rings, the thermal expansion effect dominates when the service time is less than 20 days, and the stress relaxation effect prevails when it is greater than 20 days. The higher the temperature, the more significant the stress relaxation, and the faster the leakage rate of O-rings. Increasing the fluid pressure enhances the relaxation effect. Using the maximum allowable leakage rate as the failure criterion, a pressure-temperature curve is plotted representing the safety boundaries, which can be used to guide the design of the sealing structures. Furthermore, an exhaustive study on the service life evaluation shows that at high temperature (T ≥ 120 ℃), the service life curves show a plunging segment near a pressure rise to 0.42 MPa.