A combined probabilistic analysis method on structural durability and damage tolerance is presented for multiple site damage-prone structure to analyze the flight structure service life and reliability in the same time. The probabilistic fracture mechanics method is used in the durability analysis. A series reliability model is presented to get a conservative estimation of economic service life under given reliability requirement. Monte-Carlo simulations are conducted in conjunction with a three-parameter lognormal probability distribution for the residual life of a structure. The reliability of the structure under different crack propagation life is obtained through life interference model. The feasibility of the method is validated with a numerical example of a collinear porous plate.