Wetland ecosystem services in the Canadian Prairie are under threat from anthropogenic stressors including wetland drainage. We employed a virtual watershed–based approach to investigate how some of these services respond to wetland drainage and climate change across different watershed classes in the region. Watershed class sensitivity was variable, with Pothole Till and Pothole Glaciolacustrine having higher wetland density and being the most sensitive. Our predictions indicated that peak flow and total phosphorus export would increase with wetland drainage and future precipitation increases, posing a risk of downstream water quality pollution. Conversely, these ecosystem service indicators would decrease with rising temperature across all watershed classes. Populations of both dabbling ducks and wetland-associated birds were projected to decline in response to wetland drainage and rising temperature, whereas they were expected to increase with precipitation. The number of breeding ducks and wetland-associated birds was predicted to be reduced by half due to a loss of wetland area ranging from 20 to 40% across all watershed classes. Among the dabbling ducks, Mallard and Blue-winged teal exhibited the highest sensitivity to wetland drainage. The insights from the study on the alteration of ecosystem services resulting from wetland drainage and climate change are expected to guide the efficient management of water resources and agricultural activities in the Canadian Prairie.