Plague is a flea-vectored disease introduced to North America c. 1900. It is lethal to many American mammal species, causes major die-offs (epizootics) in some populations, and may be ecologically disruptive even at lower interepizootic (enzootic) levels of transmission. We sought to determine the effects of enzootic plague on survival of Mexican woodrats (Neotoma mexicana) and to test the hypothesis that the causative bacterium Yersinia pestis can be maintained by a highly plague-susceptible species like these woodrats. We compared apparent survival for woodrats in groups with and without plague management. Woodrat groups were (1) treated for vector control with an insecticide (deltamethrin), (2) vaccinated against plague, (3) treated with both vaccine and vector control, and (4) without plague management treatments. Flea prevalence on woodrats was reduced >90% in response to deltamethrin. Apparent survival during May–September, 2010, was 31.1% for non-vaccinated adult woodrats living in deltamethrin-treated nests, compared to 9.6% for woodrats in non-treated nests. During May–September of 2010 and 2011, vaccinated juvenile woodrat survival was 16.8%, compared to 8.4% for non-vaccinated juveniles. Peak numbers of woodrats captured were 139 for the first trapping session of 2010 and 76 for the first session of 2011, suggesting a population decline consistent with the relatively low estimated survival rates. Survival results suggest that this highly plague-susceptible species can locally maintain enzootic plague while encountering substantial rates of mortality.