A new approach for progressive failure and reliability analysis of carbon fiber reinforced polymeric (CFRP) composite pressure vessel with many base random variables is developed in the paper. The elastic constants of CFRP lamina and geometric parameters of the vessel are selected as the base design variables. CFRP lamina specimen and pressure vessel were manufactured and tested in order to obtain statistics of design variables. The limit state function for progressive failure analysis was set up. Then the progressive failure and reliability analysis of the vessel were performed according to the stiffness degradation model based on Monte Carlo simulation procedure using MATLAB. The distributions of failure loads and the probability of failure of the vessel were obtained. The feasibility and accuracy of the proposed method is validated by good agreement between the simulation and experimental results. Further analysis indicates that the lamina tensile strength in the fiber direction and hoop layer thickness of the vessel have significant influence on the probability of failure of composite pressure vessel.