Mechanical reliabilities of membrane electrode assemblies (MEA) in polymer electrolyte fuel cells (PEFCs) are a major concern to fuel cell vehicles. Hygro-thermal cyclic conditions induce the mechanical stress in MEA and cracks are formed under operating conditions. The purpose of this paper is to understand the failure mechanism of MEA under several mechanical and environmental conditions for the critical design of durable PEFCs. We carried out both static tensile tests and low cycle fatigue tests for MEA. For tensile tests, temperature and humidity in a test chamber were controlled and the surface crack formation of MEA was observed by a video micro scope in situ. Low cycle fatigue tests were carried out in room condition and the number of cycles to crack formation was measured. The results showed that the mechanical properties of MEA were influenced by temperature and humidity. The observations of MEA during tensile tests revealed that cracks were formed on the surface of catalyst layers just after the yielding of MEA. This result indicates that the deformation mismatch between catalyst layer and proton exchange membrane (PEM) is an important parameter to suppress the crack formation in MEA. The results of low cycle fatigue tests revealed that the fatigue strength of MEA followed the Coffin-Manson law and the fatigue design of MEA based on the Coffin-Manson law is possible. This result is valuable for the critical design of durable PEFCs.