The present study investigates both experimentally and theoretically the effects on fuel cell performance of non-uniform porosity and permeability in the gas diffusion layer (GDL) due to clamping force. In the experimental study, various kinds of gaskets are used to simulate various compression ratios of the GDL. In the theoretical simulations, a relevant GDL compressed model and a three-dimensional proton exchange membrane (PEM) fuel cell model are developed to simulate multi-physic transport based on code from the Computational Fluid Dynamics Research Corporation (CFDRC). The results of the numerical simulations are compared and show good agreement with the experiments for performance. Further detailed investigations are made comparing the non-uniform model with the conventional uniform compression model. Although both models yield almost the same performance, their local distribution characteristics are far different such that the uniform compressed model cannot predict the local phenomena. Specifically, the distributions of temperature, species, current density and saturation are found to be highly oscillating between the rib and channel locations. Overall, the higher the compression ratio is, the better the cell performance and the larger the fluctuation amplitude. Finally, the higher the compression ratio is, the greater the saturation, water flooding and hydrogen deficiency downstream.