Recently, short-side chain (SSC) ionomer binders have been reported to improve the initial performance of polymer electrolyte fuel cells (PEFCs) by giving more uniform ionomer coats on the catalyst surface, particularly in a highly graphitized carbon support, compared with the long-side chain (LSC) ionomer binders in catalyst layers. The uniform coating property of the SSC ionomer binder improves the performance of the PEFCs by increasing the proton conductivity of the catalyst layer, particularly under low humidification conditions. The study on the SSC ionomer binder has been actively carried out from the perspective of the improvement of initial performance of PEFCs. However, the study on the SSC ionomer binder from the perspective of the durability of PEFCs has hardly been performed. In this study, the effect of structural characteristics of ionomer binders on the durability of PEFCs was investigated. In particular, the degradation behavior of different ionomer-based catalyst layers was observed with different humidification conditions. The cathode catalyst layers were fabricated by using three types of ionomer binders with the side chain length and ion exchange capacity (IEC) value as variables. The durability behavior of the PEFC MEA was studied using the catalyst and catalyst support accelerated degradation test (ADT) protocols with different humidification conditions. The catalyst used for the preparation of the MEA was Pt/C (TEC10E50E) and the ionomer binder was LSC (IEC 1.00), SCC (IEC 1.02, 1.39). The ADT was conducted according to the DOE protocol (catalyst ADT: between 0.6 and 1.0 V, 50 mV/s, catalyst support ADT: between 1.0 and 1.5 V, 500 mV/s). The degradation phenomena of the cathode catalyst layer were measured by electrochemical analysis. The change of the electrochemically active surface area (ECSA) of Pt and that of the proton conductivity of the catalyst layer were measured. The corrosion of the catalyst support was measured by measuring the catalyst layer thickness change by SEM. The detailed analysis of degradation behavior of MEAs depending on the ionomer binders and RH conditions will be discussed.