The coupling of multiple physical processes such as gas multi-component transport, gas–liquid multiphase flow, and electrochemical reactions within the proton exchange membrane fuel cell (PEMFC) makes its hydrothermal management exceptionally complicated. Therefore, the complex heat and mass transfer processes in the full-scale PEMFC are investigated in single cell with single channel serpentine flow field (FF). Firstly, the reliability of the proposed three-dimensional (3D) computational fluid dynamics (CFD) numerical model is verified by using the experimental test results of a single cell. Among them, the trend of simulation and experiment performance curves is consistent, and the minimum error of current density is 0.665%. Secondly, the ionomer model of cathode catalyst layer (CCL) is considered in CFD simulation, which is closer to the actual working condition of fuel cell (FC). The resistance of ionomer film and liquid water film mainly affects the diffusion rate of oxygen in CCL, resulting in a decrease in both current density values and power density values. Subsequently, the electrochemical reaction platform of one-dimensional (1D) FC is constructed, and the performance curves of multi-scale FCs are analyzed. The results demonstrate that the error of stack level is the largest, followed by single cell and single channel is the smallest. Finally, the 1D numerical model and the 3D PEMFC multiphase flow CFD model are utilized to investigate the cell voltage losses in the bionic spider flow field, the variable path flow field, and the serpentine flow field, respectively, under different operating conditions.