The world is changing, in terms of both climate and socio-economics. These changes have the potential to have a profound impact on the health of humans, animals and the environment, often grouped together as ‘One Health’. Humans, animals and the environment are closely interlinked and to determine realistic future vulnerabilities we must consider everything together. We need comprehensive scenarios which cover a broad range of variables affecting One Health. We developed a methodology to create national-level One Health scenarios based on the global Shared Socio-economic Pathways (SSPs), which we applied to the Netherlands. We identified variables which should be included in such scenarios and gathered input from existing scenarios, stakeholder consultation and current plans and commitments. This information was combined to create detailed descriptions, which were used to assess the main health risks under each scenario. All the scenarios face similar challenges, for example an aging population, introductions of infectious diseases and rising sea-levels and extreme weather events; however, in some scenarios, they deal with these challenges much better than in others. The healthiest outcome was achieved when a policy of low greenhouse gas emissions was combined with a well-functioning society which looks after both its citizens and the environment. These scenarios can be used to analyse specific health risks and to consider options for mitigation and preparedness. Because they are national-level scenarios, they allow the local context, policies and customs to be accounted for and should be a valuable tool for protecting One Health in the future.