Temperature and relative humidity (hygrothermal) cycles during PEM fuel cell operation can lead to the introduction and exacerbation of micro‐scale mechanical defects. We developed a two‐dimensional finite element model based on cohesive zone theory to describe the delamination propagation at the cathodic membrane/catalyst layer interface due to temperature and hygrothermal duty cycles. Particularly, the effects of hygrothermal cycle amplitudes, relative humidity (RH) distribution profiles, and gas flow channel position were studied. It was found that doubling the hygrothermal cycle amplitude resulted in a 6‐fold increase in fatigue stresses, and a defect length growth to 0,1 mm before reaching the end of the fuel cell life (40,000 cycles). A counter intuitive result was also observed, whereby a crack located within the membrane was found to grow faster than a delamination located at the catalyst layer/membrane interface. When introducing an anode/cathode channel offset, a 2‐fold increase in the rate of delamination propagation was found compared to the case with the aligned anode and cathode channels.