Canine Distemper Virus (CDV) is a multi-host morbillivirus that infects virtually all Carnivora and a few non-human primates. Here we describe a CDV outbreak in an exotic felid rescue center that led to the death of eight felids in the genus Panthera. Similar to domestic dogs and in contrast to previously described CDV cases in Panthera, severe pneumonia was the primary lesion and no viral antigens or CDV-like lesions were detected in the central nervous system. Four tigers succumbed to opportunistic infections. Viral hemagglutinin (H)-gene sequence was up to 99% similar to strains circulating contemporaneously in regional wildlife. CDV lesions in raccoons and skunk were primarily encephalitis. A few affected felids had at least one previous vaccination for CDV, while most felids at the center were vaccinated during the outbreak. Panthera sharing a fence or enclosure with infected conspecifics had significantly higher chances of getting sick or dying, suggesting tiger-tiger spread was more likely than recurrent spillover. Prior vaccination was incomplete and likely not protective. This outbreak highlights the need for further understanding of CDV epidemiology for species conservation and public health.