Many premature failures in proton exchange membrane (PEM) fuel cells are attributed to crossover of the reactant gas from microcracks in the membranes. The formation of these microcracks is believed to result from chemical and/or mechanical degradation of the constrained membrane during fuel cell operation. By characterizing the through-membrane leakage, we report failures resulting from crack formation in several PEMs mounted in fuel cell fixtures and mechanically stressed as the environment was cycled between wet and dry conditions in the absence of chemical potential. The humidity cycling tests also show that the failure from crossover leaks is delayed if membranes are subjected to smaller humidity swings. To understand the mechanical response of PEMs constrained by bipolar plates and subjected to changing humidity levels, we use Nafion® NR-111 as a model membrane and conduct numerical stress analyses to simulate the humidity cycling test. We also report the measurement of material properties required for the stress analysis—water content, coefficient of hygral expansion, and creep compliance. From the creep test results, we have found that the principle of time-temperature-humidity superposition can be applied to Nafion® NR-111 to construct a creep compliance master curve by shifting individual compliance curves with respect to temperature and water content. The stress prediction obtained using the commercial finite element program ABAQUS ® agrees well with the stress measurement of Nafion® NR-111 from both tensile and relaxation tests for strains up to 8%. The stress analysis used to model the humidity cycling test shows that the membrane can develop significant residual tensile stress after humidity cycling. The result shows that the larger the humidity swing and/or the faster the hydration/dehydration rate, the higher the residual tensile stress. This result is confirmed experimentally as PEM failure is significantly delayed by decreasing the magnitude of the relative humidity cycle. Based on the current study, we also discuss potential improvements for material characterization, material state diagnostics, and a stress model for PEMs.