A mathematical multilayer, multispecies two-phase model for polymer electrolyte fuel cells (PEFCs) is presented based on fundamental molecular theory using the general transport equation (GTE). The GTE was previously developed and applied to bridge the gap that exists between the benchmark modeling philosophies in the literature for transport across the PEFC. In the current work, the GTE is applied with Darcy’s law to describe water transport and water uptake through the porous and quasiporous layers of a PEFC under single- and two-phase operating conditions. The characteristic transport equations and available material properties from the literature are translated into a single-cell fuel cell model, which is implemented using the object modeling technique. The PEFC model is applied to predict and validate the net water transport ratio and water content under a range of operating conditions. The numerical model exhibits good agreement with experimental data under both vapor- and liquid-equilibrated conditions. The model is then applied in a water transport study to determine the effects of cell compression on local water content, liquid water intrusion, water transport, and Ohmic resistance across nonreinforced polymer electrolyte membranes (PEMs) under two-phase operating conditions. The modeling results suggest that the presence of liquid water at the cathodic boundary of the PEM and a well-established liquid water network can affect water uptake and water transport and can reduce the Ohmic resistance of the PEM.