Most generally used flow channel designs in polymer electrolyte membrane fuel cells (PEMFCs) are serpentine flow designs as single channels or as multiple channels due to their advantages over parallel flow field designs. But these flow fields have inherent problems of high pressure drop, improper reactant distribution, and poor water management, especially near the U-bends. The problem of inadequate water evacuation and improper reactant distribution become more severe and these designs become worse at higher current loads (low voltages). In the current work, a detailed performance study of enhanced cross-flow split serpentine flow field (ECSSFF) design for PEMFC has been conducted using a three-dimensional (3-D) multiphase computational fluid dynamic (CFD) model. ECSSFF design is used for cathode part of the cell and parallel flow field on anode part of the cell. The performance of PEMFC with ECSSFF has been compared with the performance of triple serpentine flow design on cathode side by keeping all other parameters and anode side flow field design similar. The performance is evaluated in terms of their polarization curves. A parametric study is carried out by varying operating conditions, viz, cell temperature and inlet humidity on air and fuel side. The ECSSFF has shown superior performance over the triple serpentine design under all these conditions.