Mean water depth and range of interannual water-level fluctuations over wet-dry cycles in precipitation are major drivers of vegetation zone formation in North American prairie potholes. We used harmonic hydrological models, which require only mean interannual water depth and amplitude of water-level fluctuations over a wet–dry cycle, to examine how the vegetation zones in a pothole would respond to small changes in water depth and/or amplitude of water-level fluctuations. Field data from wetlands in Saskatchewan, North Dakota, and South Dakota were used to parameterize harmonic models for four pothole classes. Six scenarios in which small negative or positive changes in either mean water depth, amplitude of interannual fluctuations, or both, were modeled to predict if they would affect the number of zones in each wetland class. The results indicated that, in some cases, even small changes in mean water depth when coupled with a small change in amplitude of water-level fluctuations can shift a prairie pothole wetland from one class to another. Our results suggest that climate change could alter the relative proportion of different wetland classes in the prairie pothole region.