Interdisciplinary research on zoonotic disease has tended to focus on ‘risk’ of disease transmission as a conceptual common denominator. With reference to endemic zoonoses at the livestock-human interface, we argue for considering a broader sweep of disciplinary insights from anthropology and other social sciences in interdisciplinary dialogue, in particular cross-cultural perspectives on human-animal engagement. We consider diverse worldviews where human-animal encounters are perceived of in terms of the kinds of social relations they generate, and the notion of culture is extended to the ‘natural’ world. This has implications for how animals are valued, treated and prioritized. Thinking differently with and about animals and about species’ boundaries could enable ways of addressing zoonotic diseases which have closer integration with people’s own cultural norms. If we can bring this kind of knowledge into One Health debates, we find ourselves with a multiplicity of worldviews, where bounded categories such as human:animal and nature:culture cannot be assumed. This might in turn influence our scientific ways of seeing our own disciplinary cultures, and generate novel ways of understanding zoonoses and constructing solutions.