Abstract Proton exchange membrane fuel cells (PEMFCs) have emerged as a promising solution as the world is moving toward sustainable energy resources. However, in order to compete economically with existing technologies, further improvements in performance are necessary. Mathematical modeling and optimization are viable tools for designing better PEMFCs. This study aims to provide a framework for topological optimization of the electrode structure, with the ultimate goal of enhancing cell performance. To achieve this, a two-phase flow model of PEMFC is developed to characterize the cell performance. The model is then coupled with a topology optimization technique, which is the main focus of the present work, to seek an optimized constituent distribution in the catalyst layer. Results indicate that an electrode with a heterogeneous structure can enhance the overall cell performance by balancing various transport and rate processes. The optimized designs are investigated for various key factors, including effective diffusivity, effective conductivity, and liquid water management, to demonstrate how an optimized design can be advantageous.