The clamping pressure used in assembling a proton exchange membrane (PEM) fuel cell stack can have significant effects on the overall cell performance. The pressure causes stack deformation, particularly in the gas diffusion layer (GDL), and impacts gas mass transfer and electrical contact resistance. Existing research for analyzing the assembly pressure effects is mostly experimental. This paper develops a sequential approach to study the pressure effects by combining the mechanical and electrochemical phenomena in fuel cells. The model integrates gas mass transfer analysis based on the deformed GDL geometry and modified parameters with the microscale electrical contact resistance analysis. The modeling results reveal that higher assembly pressure increases cell resistance to gas mass transfer, causes an uneven current density distribution, and reduces electrical contact resistance. These combined effects show that as the assembly pressure increases, the PEM fuel cell power output increases first to a maximum and then decreases over a wide range of pressures. An optimum assembly pressure is observed. The model is validated against published experimental data with good agreements. This study provides a basis for determining the assembly pressure required for optimizing PEM fuel cell performance.