We present a comprehensive theoretical and experimental study of the effect of membrane thickness on the anion-exchange membrane (AEM) fuel cell (AEMFC) performance. AEMFC tests are carried out with several AEMs with thickness in the range of 5 – 50 µm and assembled with a PtRu anode, and two different cathode catalysts (Pt/C or Fe-N-C). Dramatic improvements in cell performance are observed as the membrane thickness decreases, which is mainly attributed to reduced ohmic losses and enhanced water transport between the electrodes. The simulated cell performance obtained using our previously developed AEMFC model qualitatively and quantitatively explains the experimental results in the entire range of current densities (0-4 Acm-2). Simulated results show that thinner membranes enhance water transport between the electrodes, mitigating the anode flooding, and resulting in increased local hydration in the membrane and cathode catalytic layer. These high hydration values enhance the anionic conductivity of the ionomeric materials, thereby improving cell performance. Furthermore, the enhanced water transport towards the cathode electrode provides sufficient water to participate in the oxygen reduction reaction, thus reducing the activation losses. Simulation modeling allows for a thorough understanding of cell behavior and aids in the development of the next generation of advanced AEMFCs