Habitat loss and degradation appear to be the primary drivers of amphibian declines. Given the losses of native prairie and prairie wetlands, it is essential to understand the habitat conditions that support amphibian species in remaining prairie ecosystems. In this study, we combine wetland surveys, geographic information systems (GIS), and hierarchical statistical modeling to assess anuran occupancy relationships with wetland and landscape factors. We surveyed 141 wetlands with repeated sampling for amphibian breeding activity (calling, eggs, tadpoles, metamorphs) in the Sheyenne National Grasslands—one of the largest contiguous prairies on the North American continent. Overall we observed evidence of seven amphibian species breeding in the Sheyenne National Grasslands. Species with ubiquitous distributions (Boreal Chorus Frogs) or species that occurred infrequently (Canadian Toads and Great Plains Toads) had little variance in occupancy. However, Northern Leopard Frogs, Wood Frogs, and Gray Treefrogs exhibited occupancy relationships with wetland and landscape variables. Our results establish a baseline understanding of current prairie amphibian–habitat relationships. Furthermore, they indicate that integrating local and landscape variables into occupancy models that account for spatial autocorrelation can provide a better understanding of amphibian ecology, and can inform conservation and restoration programs.