Understanding mesocarnivore responses to both natural and anthropogenic disturbance is crucial for understanding species' potential to maintain landscape persistence into the future. We examined the response of five mesocarnivore species (bobcat, coyote, fisher, gray fox, and red fox) to both types of disturbances and climatic conditions. The Northeastern U.S. has experienced multiple large‐scale disturbances, such as a mass defoliation event following larval spongy moth outbreak and high densities of infrastructure that divide the natural landcover into roadless zones where these species inhabit. Using dynamic occupancy models in a Bayesian framework, we aimed to (1) examine variation in species' responses over a 4‐year study by estimating variation in site‐level occupancy, colonization and extirpation of each species in the state of Rhode Island relative to natural disturbance (i.e., defoliation event), anthropogenic disturbance (i.e., parceling of natural landcover bounded by roads, distance to roads), and climate (i.e., seasonal precipitation) and (2) compare current occurrence trends to predicted asymptotic occupancy to identify key variables contributing to distribution instability. Our findings indicated declines in the occurrence of both fox species, and fisher. There was variation in mesocarnivore response to disturbance among the species. We found gray fox and fisher occupancy dynamics to be sensitive to all forms of disturbance and coyote occurrence was positively associated with anthropogenic disturbance. Although bobcat and red fox were predicted to respond positively to future climate scenarios, fisher and gray fox were not, and persistence of fisher and gray fox in a landscape of disturbance relies on large areas with high forest and shrubland cover. With the wide‐spread spongy moth outbreak across much of southern New England, our findings indicate that efforts to conserve forested lands may be crucial in maintaining the persistence of several mesocarnivore species in this region experiencing large‐scale disturbance.