The spatial distribution of prairie dog (Cynomys ludovicianus) colonies in North America has changed from large, contiguous populations to small, isolated colonies in metapopulations. One factor responsible for this drastic change in prairie-dog population structure is plague (caused by the bacterium Yersinia pestis). We fit stochastic patch occupancy models to 20 years of prairie-dog colony occupancy data from two discrete metapopulations (west and east) in the Pawnee National Grassland in Colorado, USA, that differ in connectivity among suitable habitat patches. We conducted model selection between two hypothesized modes of plague movement: independent of prairie-dog dispersal (colony-area) vs. plague movement consistent with prairie-dog dispersal (connectivity to extinct colonies). The best model, which fit the data well (area under the curve [AUC]: 0.94 west area; 0.79 east area), revealed that over time the proportion of extant colonies was better explained by colony size than by connectivity to extinct (plagued) colonies. The idea that prairie dogs are not likely to be the main vector that spreads Y. pestis across the landscape is supported by the observation that colony extinctions are primarily caused by plague, prairie-dog dispersal is short range, and connectivity to extinct colonies was not selected as a factor in the models. We also conducted simulations with the best model to examine long-term patterns of colony occupancy and persistence of prairie-dog metapopulations. In the case where the metapopulations persist, our model predicted that the western metapopulation would have a colony occupancy rate approximately 2.5 times higher than that of the eastern metapopulation (-50% occupied colonies vs. 20%) in 50 years, but that the western metapopulation has -80% chance of extinction in 100 years while the eastern metapopulation has a less than 25% chance. Extinction probability of individual colonies depended on the frequency with which colonies of the same size class occurred in the metapopulation. Thus, the long-term persistence of prairie-dog metapopulations depended on specific details of the metapopulation.