High-temperature proton exchange membrane fuel cells (HT-PEMFCs) could replace fossil fuel-based technologies for applications which cannot involve bulky/heavy cooling systems, such as aeronautics. However, severe materials degradations upon operation prevent performance retention for acceptable lifetimes. While others have already reported degradations in HT-PEMFC, post mortem characterizations of used HT-PEMFC membrane electrode assemblies (MEAs) remain scarce. Herein, HT-PEMFC performance degradation is studied by applying a startup/shutdown protocol to a short-stack operated at 160 °C; one MEA is characterized using complementary physicochemical/electrochemical techniques to identify/understand the degradation mechanisms and their origin. This start/stop operation mode (co-flow gas reactants) leads to substantial degradation inhomogeneity. For the anode, migration, coalescence, and detachment of Pt nanoparticles are witnessed induced by high-surface-area carbon support functionalization and corrosion. The anode electrochemical surface area (ECSA) remains constant at the inlet and increases significantly at the outlet, following inhomogeneous degradation of the cathode catalyst: the Pt z+ ions formed at high potential/oxidizing conditions concentrate towards the outlet, where they redeposit locally or at the anode, after diffusion/migration across the PBI membrane. Hence, the cathode ECSA decreases significantly at the inlet. Furthermore, intense Ni-leaching from the initial PtNi alloy catalyst is reported as a result of O 2 mass-transport and phosphoric acid dilution inhomogeneity.