One Health, an integrated health concept, is now an integral part of health research and development. One Health overlaps with other integrated approaches to health such as EcoHealth or Planetary Health, which not only consider the patient or population groups but include them in the social-ecological context. One Health has gained the widest foothold politically, institutionally, and in operational implementation. Increasingly, One Health is becoming part of reporting under the International Health Legislation (IHR 2005). The Swiss Tropical and Public Health Institute (Swiss TPH) has played a part in these developments with one of the first mentions of One Health in the biomedical literature. Here, we summarise the history of ideas and processes that led to the development of One Health research and development at the Swiss TPH, clarify its theoretical and methodological foundations, and explore its larger societal potential as an integrated approach to thinking. The history of ideas and processes leading to the development of One Health research at the Swiss TPH were inspired by far-sighted and open ideas of the directors and heads of departments, without exerting too much influence. They followed the progressing work and supported it with further ideas. These in turn were taken up and further developed by a growing number of individual scientists. These ideas were related to other strands of knowledge from economics, molecular biology, anthropology, sociology, theology, and linguistics. We endeavour to relate Western biomedical forms of knowledge generation with other forms, such as Mayan medicine. One Health, in its present form, has been influenced by African mobile pastoralists’ integrated thinking that have been taken up into Western epistemologies. The intercultural nature of global and regional One Health approaches will inevitably undergo further scrutiny of successful ways fostering inter-epistemic interaction. Now theoretically well grounded, the One Health approach of seeking benefits for all through better and more equitable cooperation can clearly be applied to engagement in solving major societal problems such as social inequality, animal protection and welfare, environmental protection, climate change mitigation, biodiversity conservation, and conflict transformation.