Due to the degradation of material and relaxation of contact stress, the deterioration of sealing performance of bolted flange connection usually occurs, especially when it works under high temperature. Also, the sealing performance is significantly affected by the unevenness of contact stress and temperature distributions in the gasket. To improve the prediction precision of leakage rate, a time-dependent leakage prediction model for bolted flange connections is established in this work, considering the unevenness of contact stress and temperature distribution. The methods for computing equivalent stress and temperature are proposed with respect to the radius-dependent stress and temperature distribution in the gasket. As an example, finite element analysis is carried to obtain the temperature and stress distributions of flexible graphite composite gaskets in bolted flange connections. Then the experimental investigations on sealing performance and ignition loss of flexible graphite composite gasket are carried out and the equivalent contact stress in the gasket is determined. Thereby, a time-dependent leakage rate prediction method is established in consideration of the radial unevenness of contact stress and temperature.