The Prairie Pothole Region (PPR) of North America is a globally important resource that provides abundant and valuable ecosystem goods and services in the form of biodiversity, groundwater recharge, water purification, flood attenuation, and water and forage for agriculture. Numerous studies have found these wetlands, which number in the millions, to be highly sensitive to climate variability. Here, we compare wetland conditions between two 30-year periods (1946–1975; 1976–2005) using a hindcast simulation approach to determine if recent climate warming in the region has already resulted in changes in wetland condition. Simulations using the WETLANDSCAPE model show that 20th century climate change may have been sufficient to have a significant impact on wetland cover cycling. Modeled wetlands in the PPR's western Canadian prairies show the most dramatic effects: a recent trend toward shorter hydroperiods and less dynamic vegetation cycles, which already may have reduced the productivity of hundreds of wetland-dependent species.