We report a multi-paradigm model of the membrane chemical degradation in Polymer Electrolyte Membrane Fuel Cells (PEMFCs), by combining Coarse-Grained Molecular Dynamics (CGMD) and a multiscale cell performance model. CGMD is used to generate structural databases that relate the amount of detached (degraded) ionomer sidechains with the water content and the resulting PEM meso-microporous structure. The multiscale cell performance model describes the electrochemical reactions and transport mechanisms occuring in the electrodes from an on-the-fly coupling between Kinetic Monte Carlo (KMC) sub-models parametrized with Density Functional Theory (DFT) data and (partial differential equations-based) continuum sub-models. Furthermore, the performance model includes a kinetic PEM degradation sub-model which integrates the CGMD database. The cell model also predicts the instantaneous PEM sidechain content and conductivity evolution at each time step. The coupling of these diverse modeling paradigms allows one to describe the feedback between the instantaneous cell performance and the intrinsic membrane degradation processes. This provides detailed insights on the membrane degradation (sidechain detachment as well as water reorganization within the PEM) during cell operation. This novel modeling approach opens interesting perspectives in engineering practice to predict materials degradation and durability as a function of the initial chemical composition and structural properties in electrochemical energy conversion and storage devices. From the second half of the twentieth century, Polymer Electrolyte Membrane Fuel Cells (PEMFCs) have attracted much attention due to their potential as a clean power source for vehicles traction. Market introduction of FC vehicles is being recognized of highest priority in many developed countries due to their impact on the reduction of energy consumption and greenhouse gas emissions. However, PEMFC technologies have not yet reached all the requirements to be competitive, in particular regarding their high production cost of Membrane Electrode Assemblies and their low durability.Indeed, meso/micro-structural degradation leading to the PEMFC components aging is attributed to several complex physicochemical mechanisms not yet completely understood. The associated components meso/micro-structural changes translate into irreversible longterm cell power degradation.1-3 For instance, dissolution and redistribution of the catalyst reduces the specific catalyst surface area and the electrochemical activity. The corrosion of the catalyst carbon-support and loss or decrease of the hydrophobicity caused by an alteration of the Polytetrafluoroethylene in Catalyst Layers (CLs), Microporous Layers and Gas Diffusion Layers also affect the water management in the cell and thus the electrochemical performance.Regarding the polymer electrolyte in PEMFCs, a large number of materials has been tested, including sulfonated hydrocarbon polymers, phosphoric acid doped polybenzimidazole, polymer-inorganic composit...