The microbiomes of plants can modulate the impacts of pests, including through interactions with microbiomes of pathogen vectors such as ambrosia beetles. While physical and chemical traits of plant hosts are known to affect beetle-carried microbes, how beetle and host microbiomes interact is seldom explored. We aimed to determine whether wood-inhabiting endophytes mediate host susceptibility to Fusarium dieback, an emergent tree disease complex that includes ambrosia beetle vectors. We studied three competent host tree species (Persea americana, Salix spp., Platanus racemosa) common in disease hot spots in agricultural and wildland habitats. Using culturing methods, we compared wood microbiomes of 319 attacked and 133 non-attacked trees across a network of 47 beetle-infested and 41 non-infested plots in southern California, USA. We conducted 1,148 in vitro assays to evaluate antagonism by wood-inhabiting endophytic fungi (60 species) and bacteria (40 species) to the Fusarium pathogens, finding 15 fungal and 11 bacterial species with clear antagonism to the pathogen. Such wood endophytes may potentially protect tree hosts as biological control agents. Antagonistic microbes were more common in attacked trees than in non-attacked trees, suggesting the abundance of antagonistic fungi and bacteria in the wood is insufficient to determine host susceptibility to attack or they are enriched in attacked trees. Wood-inhabiting microbial communities were consistently different between cultivated P. americana and wildland tree species, as there were some differences based on host attack status. Differences between attacked and non-attacked trees were reflected in different microbial consortia rather than the abundance of individual, antagonistic microbial species.