ABSTRACTExamination of the host‐associated microbiome in wildlife can provide critical insights into the eco‐evolutionary factors driving species diversification and response to disease. This is particularly relevant for isolated populations lacking genomic variation, a phenomenon that is increasingly common as human activities create habitat ‘islands’ for wildlife. Here, we characterised the gut and otic microbial communities of one such species: Channel Island foxes (Urocyon littoralis). The gut microbiome provided evidence of phylosymbiosis by reflecting the host phylogeny, geographic proximity, history of island colonisation and contemporary ecological differences, whereas the otic microbiome primarily reflected geography and disease. Santa Catalina Island foxes are uniquely predisposed to ceruminous gland tumours following infection with Otodectes cynotis ear mites, while San Clemente and San Nicolas Island foxes exhibit ear mite infections without evidence of tumours. Comparative analyses of otic microbiomes revealed that mite‐infected Santa Catalina and San Clemente Island foxes exhibited reduced bacterial diversity, skewed abundance towards the opportunistic pathogen Staphylococcus pseudintermedius and disrupted microbial community networks. However, Santa Catalina Island foxes uniquely harboured Fusobacterium and Prevotella bacteria as potential keystone taxa. These bacteria have previously been associated with colorectal cancer and may predispose Santa Catalina Island foxes to an elevated cancer risk. In contrast, mite‐infected San Nicolas Island foxes maintained high bacterial diversity and robust microbial community networks, suggesting that they harbour more resilient microbiomes. Considered together, our results highlight the diverse eco‐evolutionary factors influencing commensal microbial communities and their hosts and underscore how the microbiome can contribute to disease outcomes.