Stack reliability is of great importance in commercialization of vanadium redox flow battery (VFB) since practical VFB stacks are prone to undergo material failure and electrolyte leakage caused by unreliable stack design and improper assembling conditions. A comprehensive evaluation of mechanical behavior and analysis of stack failure is thus highly valued for material fabrication, stack design and assembly. In this study, mechanical behavior and Weibull statistics based failure analysis of the VFB stacks are investigated. The Weibull parameters of two key components are firstly determined from tensile strength tests, which, in combination with finite element analysis of the stack mechanical behavior, are subsequently used to calculate the stack failure probability at specified clamping forces for two different stack designs that both contains 20 individual cells. The results demonstrate that the stack failure probability can be significantly reduced by properly decreasing the clamping forces for both designs, while adding a thick plate to the middle of the stack can effectively lower the probability of failure thus offering a superior stack mechanical performance and a prolonged stack life cycle. Such an approach to analyze stack failure can be readily accessed by flow battery engineers for design and assembly of commercial VFB stacks.