Wetlands worldwide are under threat from anthropogenic impacts. In large protected North American areas such as Yellowstone and Wood Buffalo National Parks, aquatic habitats are disappearing and wetland-dependent fauna are in decline1-3. Here we investigate population dynamics of an indicator species in Canada's Peace-Athabasca Delta ("the delta"), a World Heritage Site. Based on population surveys, habitat mapping and genetic data from 288 muskrats, we use agent-based modeling and genetic analyses to explain population expansion and decline of the semi-aquatic muskrat (Ondatra zibethicus). Simulations quantify a large population (~500,000 individuals) following flood-induced habitat gains, with decreased size (~10,000 individuals) during drying. Genetic analyses show extremely low long-term effective population size (Ne: 60-127), supporting a legacy of population bottlenecks. Our simulations indicate that the muskrat population in the delta is a metapopulation with individuals migrating preferentially along riparian pathways. Related individuals found over 40 km apart imply dispersal distances far greater than their typical home range (130 m). Rapid metapopulation recovery is achieved via riparian corridor migration and passive flood-transport of individuals. Source-sink dynamics show wetland loss impacts on the muskrat metapopulation's spatial extent. Dramatic landscape change is underway, devastating local fauna, including this generalist species even in a protected ecosystem.