The prairie pothole physiographic region of North America is likely to be affected by climate change, and it is important to establish its baseline global warming potential as a basis for assessing global change effects. This study estimated the hydrologic effects on soil greenhouse gas efflux during the growing season along hydrologic profiles within natural prairie potholes ranging from the southern to northern limits of the prairie pothole region within central Canada. Soil moisture was found to be an important driver of differences in soil efflux along the hydrologic profiles and along the south-to-north gradient. The position of peak cumulative soil efflux varied along the hydrologic profile, with the N2O peak occurring at the backslope, the CO2 peaks at footslope and toeslope, and the CH4 peaks at toeslope and surface waters. When cumulative soil efflux was converted to global warming potential (Mg CO2 eq), the largest values were restricted to the narrow land-water interface in the south but expanded to a broader area of the hillslope in the north. CO2 was the major (> 95%) contributor to global warming potential. Omitting hydrologic controls on greenhouse gas fluxes from estimates of global warming potential led to substantial underestimates of the contributions of N2O and CH4. Arid regions in the south had smaller global warming potential than wetter regions in the north. If future climate projections for a warmer, drier climate in this region are realized, global warming potential from soil greenhouse gas fluxes will be smaller in this landscape, because the changing hydrologic conditions should result in a reduction of global warming potential from land surfaces, even as global warming potential from surface waters increases.