Wetland ecosystems are vital for maintaining global biodiversity, as they provide important stopover sites for many species of migrating wetland‐associated birds. However, because weather determines their hydrologic cycles, wetlands are highly vulnerable to effects of climate change. Although changes in temperature and precipitation resulting from climate change are expected to reduce inundation of wetlands, few efforts have been made to quantify how these changes will influence the availability of stopover sites for migratory wetland birds. Additionally, few studies have evaluated how climate change will influence interannual variability or the frequency of extremes in wetland availability. For spring and fall bird migration in seven ecoregions in the south‐central Great Plains of North America, we developed predictive models associating abundance of inundated wetlands with a suite of weather and land cover variables. We then used these models to generate predictions of wetland inundation at the end of the century (2069–2099) under future climate change scenarios. Climate models predicted the average number of inundated wetlands will likely decline during both spring and fall migration periods, with declines being greatest in the eastern ecoregions of the southern Great Plains. However, the magnitude of predicted declines varied considerably across climate models and ecoregions, with uncertainty among climate models being greatest in the High Plains ecoregion. Most ecoregions also were predicted to experience more‐frequent extremely dry years (i.e., years with extremely low wetland abundances), but the projected change in interannual variability of wetland inundation was relatively small and varied across ecoregions and seasons. Because the south‐central Great Plains represents an important link along the migratory routes of many wetland‐dependent avian species, future declines in wetland inundation and more frequent periods of only a few wetlands being inundated will result in an uncertain future for migratory birds as they experience reduced availability of wetland stopover habitat across their migration pathways.