More than 60% of emerging infectious diseases of humans have a wildlife origin, and when these diseases spread through human populations to new geographical areas, there is a considerable risk of spillback from humans to wildlife species. Spillback events can have severe consequences for wildlife populations, where the disease may cause morbidity and mortality, and human populations, where the establishment in wildlife may lead to prolonged transmission or new exposures in humans. Mitigating these consequences requires identifying the key risk factors that lead to human–wildlife transmission events and implementing risk-reducing actions, a challenge given that cross-species transmission events are rare and often data deficient. To identify potential species and locations that are most likely to lead to these rare events, we developed a spatially explicit, rapid risk assessment framework that incorporates three components of the spillback process: wildlife susceptibility, wildlife exposure, and pathogen introduction pressure. To demonstrate the broad applicability of our framework, we conducted a rapid risk assessment on two recent emerging zoonotic pathogens in humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mpox, to determine the relative spillback risk to wild mammalian species in the continental United States. The rapid risk assessment identified both species and locations with higher than expected spillback risk, providing managers and researchers with valuable information to prioritize surveillance and risk-mitigation actions. Our framework represents a rapid and flexible approach to assess the risks of spillback to wildlife populations during rapidly evolving zoonotic disease outbreaks.