Flow distributions among proton exchange membrane fuel cell (PEMFC) stacks remain an important issue owing to the great influences on stack performances. To simultaneously consider flow distributions as well as reactions, phase changes, and transport processes inside every fuel cell, a comprehensive stack model is developed based on the integration of a 1 + 1 dimensional multiphase stack sub-model and a flow distribution sub-model. Frictional and local pressure drops due to diverging, converging, and bending configurations are calculated. After rigorous model validation, differences between the uniform flow assumption and the authentically non-uniform distribution are quantitatively investigated, including the distribution of voltage, mass flow rate, temperature, reactant concentration, and other parameters. Results show that the uniform assumption not only overestimates the stack output performance but also underestimates the cell voltage variations. Besides, the uniform assumption may lead to higher predictions of the overall stack temperature and lower predictions of temperature variations among different fuel cells. Even though the total amount of air seems abundant, it is still possible for some fuel cells to suffer from the local reactant starvation. Therefore, a higher cathode stoichiometry is preferable since it increases the inlet mass flow rate for middle cells. Increasing the inlet pressure contributes negligibly to the uniformity of reactant distribution, but it improves the stack performance. A larger manifold cross-sectional area leads to more uniform reactant distributions among the stack and less local current density variations inside single cells.