In large polymer electrolyte membrane (PEM) fuel cell stacks, monitoring and control of the local changes in membrane humidity inside the cathode channel is critical. In this study, a control-oriented dynamic model capable of describing the spatial distribution of voltage and relative humidity (RH) in a large fuel cell stack is developed and experimentally validated. The model tracks energy and mass flow inside the cathode, anode, and coolant channels, as well as the fuel cell stack body. Validation tests show that the model agrees well with the experimental data. The new modeling framework developed in this study can be used to predict the localized effects of humidity on the performance of a fuel cell stack. Also, given its accurate prediction of RH in the stack, this model can be used as an observer to predict local humidity variations that are, otherwise, not available. This capability would allow PEM fuel cells to avoid membrane damage due to low operating humidities as well as efficiency losses due to catalyst layer flooding.