Since 2021, the United States has experienced a significant increase in H5N1 (“avian flu”) infections, spreading from wild fowl to domestic poultry, dairy cattle, and some humans, primarily agricultural workers. This study examines urban-rural differences in willingness to receive an H5N1 vaccine and change dietary behavior based on potential CDC recommendations. A survey (Aug 5–15, 2024) sampled 5,000 urban and 5,000 rural participants via online panels and live operator calls. Key measures included willingness to vaccinate and change diet related to dairy or egg consumption in line with potential CDC recommendations, with residence classification as the main independent variable. Logistic regression assessed associations, controlling for demographics and health-related factors. Rural residents were more likely to have heard of bird flu but less likely to perceive it as a threat to humans generally or to themselves personally. After adjusting for sociodemographic characteristics, rural residents were less likely to be willing to change their diets due to potential CDC recommendations, but their vaccination intent relative to a potential H5N1 vaccine was on par with urban populations. Findings highlight the potential to modify behaviors in respect to consuming raw milk products and undercooked foods and accepting potential H5N1 vaccination may reflect institutional trust gaps and cultural dietary norms. Targeted public health messaging is needed to engage rural communities where the epicenters of the current outbreak are occurring.