Understanding membrane degradation induced by combined chemical and mechanical stresses is critical to designing durable polymer electrolyte membrane fuel cells. Accelerated stress tests (ASTs) are usually designed and carried out to study membrane degradation and identify stresses leading to it. In this work, a customized small-scale fuel cell fixture designed for in situ X-ray computed tomography (XCT) imaging is utilized to study the impact of different AST conditions on combined chemical and mechanical membrane durability. The XCT imaging technique allows the acquisition of a tomographic dataset yielding an integrated 3D image stack, which in turn, is used to analyze and compare global membrane degradation mechanisms. It was identified that cell temperature and relative humidity (RH) strongly influence the chemical membrane degradation rate, whereas the mechanical degradation rate was promoted by RH cycles with high amplitude and short period, which were dynamically diagnosed through a single frequency electrochemical impedance spectroscopy technique developed to track membrane hydration. When applied consecutively, the high chemical and mechanical stress intensities produced a joint chemo-mechanical failure mode with distinct evidence of chemical (thinning) and mechanical (fatigue-fracture) contributions in a relatively short time. The proposed AST is thus recommended for chemo-mechanical membrane durability evaluation in fuel cells.