Guinea worm disease (dracunculiasis) is a debilitating waterborne disease. Once widespread, it is now on the brink of eradication. However, the Guinea Worm Eradication Programme (GWEP), like guinea worm itself, has been under-studied by historians. The GWEP demonstrates an unusual model of eradication, one focused on primary healthcare (PHC), community participation, health education and behavioural change (safe drinking). The PHC movement collided with a waterborne disease, which required rapid but straightforward treatment to prevent transmission, creating a historical space for the emergence of village-based volunteer health workers, as local actors realigned global health policy on a local level. These Village Volunteers placed eradication in the hands of residents of endemic areas, epitomising the participation-focused nature of the GWEP. This participatory mode of eradication highlights the agency of those in endemic areas, who, through volunteering, safe drinking and community self-help, have been the driving force behind dracunculiasis eradication. In the twenty-first century, guinea worm has become firstly a problem of human mobility, as global health has struggled to contain cases in refugees and nomads, and latterly a zoonotic disease, as guinea worm has shifted hosts to become primarily a parasite of dogs. This demonstrates both the potential of One Health approaches and the need for One Health to adopt from PHC and the GWEP a focus on the health of humans and animals in isolated and impoverished areas. Guinea worm demonstrates how the biological and the historical interact, with the GWEP and guinea worm shaping each other over the course of the eradication programme.