Highly lethal pathogens (e.g., hantaviruses, hendra virus, anthrax, or plague) pose unique public-health problems, because they seem to periodically flare into outbreaks before disappearing into long quiescent phases. A key element to their possible control and eradication is being able to understand where they persist in the latent phase and how to identify the conditions that result in sporadic epidemics or epizootics. In American grasslands, plague, caused by Yersinia pestis, exemplifies this quiescent-outbreak pattern, because it sporadically erupts in epizootics that decimate prairie dog (Cynomys ludovicianus) colonies, yet the causes of outbreaks and mechanisms for interepizootic persistence of this disease are poorly understood. Using field data on prairie community ecology, flea behavior, and plague-transmission biology, we find that plague can persist in prairie-dog colonies for prolonged periods, because host movement is highly spatially constrained. The abundance of an alternate host for disease vectors, the grasshopper mouse (Onychomys leucogaster), drives plague outbreaks by increasing the connectivity of the prairie dog hosts and therefore, permitting percolation of the disease throughout the primary host population. These results offer an alternative perspective on plague's ecology (i.e., disease transmission exacerbated by alternative hosts) and may have ramifications for plague dynamics in Asia and Africa, where a single main host has traditionally been considered to drive Yersinia ecology. Furthermore, abundance thresholds of alternate hosts may be a key phenomenon determining outbreaks of disease in many multihost-disease systems.