Long-term durability of the membrane electrode assembly (MEA) in proton exchange membrane (PEM) fuel cells is one of the major technological barriers to the commercialization of fuel cell vehicles. The cracks in the electrode layers of the MEA, referred to as mud-cracks, are potential contributors to the failure in the PEM. To investigate how these mud-cracks affect the mechanical durability of the MEA, pressure-loaded blister tests are performed at to determine the biaxial fatigue strength of Gore-Primea® series 57 MEA. In these volume-controlled tests, leaking rate is determined as a function of fatigue cycles. The failure is defined to occur when the leaking rate exceeds a specified threshold. Postmortem characterization using bubble point testing and field emission scanning electron microscopy (FESEM) was conducted to provide visual documentation of leaking failure sites. The analysis of the experimental leaking data indicates that the MEA has much shorter lifetimes at the same nominal stress levels than membrane samples without the electrode layers. FESEM photomicrographs of leaking locations identified via the bubble point testing show cracks in the membrane that are concentrated within the mud-cracks of the electrode layer. These two pieces of information indicate that the mud-cracks within the electrode layers contribute to the leaking failures of the MEA assembly. For the fuel cell industry, this study suggests there is an opportunity to reduce the likelihood of membrane pinhole failures by reducing the size and occurrence of the mud-cracks formed during the MEA processing or by increasing the fatigue resistance (including the notch sensitivity) of the membrane material within the MEA.