One of the bottlenecks hindering the usage of polymer electrolyte membrane fuel cell technology in automotive applications is the highly load-sensitive degradation of the cell components. The cell failure cases reported in the literature show localized cell component degradation, mainly caused by flow-field dependent non-uniform distribution of reactants. The existing methodologies for diagnostics of localized cell failure are either invasive or require sophisticated and expensive apparatus. In this study, with the help of a multiscale simulation framework, a single polymer electrolyte membrane fuel cell (PEMFC) model is exposed to a standardized drive cycle provided by a system model of a fuel cell car. A 2D multiphysics model of the PEMFC is used to investigate catalyst degradation due to spatio-temporal variations in the fuel cell state variables under the highly transient load cycles. A three-step (extraction, oxidation, and dissolution) model of platinum loss in the cathode catalyst layer is used to investigate the cell performance degradation due to the consequent reduction in the electro-chemical active surface area (ECSA). By using a time-upscaling methodology, we present a comparative prediction of cell end-of-life (EOL) under different driving behavior of New European Driving Cycle (NEDC) and Worldwide Harmonized Light Vehicles Test Cycle (WLTC).