Open defecation is practiced by more than one billion people throughout the world and leads to significant public health issues including infectious disease transmission and stunted growth in children. Zambia implemented community-led total sanitation (CLTS) as an intervention to eliminate open defecation in rural areas. To support CLTS and the attainment of open defecation free communities, chiefs were considered key agents of change and were empowered to drive CLTS and improve sanitation for their chiefdom. Chiefs were provided with data on access to sanitation in the chiefdom during chiefdom orientations prior to the initiation of CLTS within each community and encouraged to make goals of universal sanitation access within the community. Using a survival regression, we found that where chiefs were orientated and mobilized in CLTS, the probability that a village would achieve 100% coverage of adequate sanitation increased by 23% (hazard ratio = , 95% confidence interval = –, P = ). Using an interrupted time series, we found a 30% increase in the number of individuals with access to adequate sanitation following chiefdom orientations (95% confidence interval = –%). The mobilization and support of chiefs greatly improved the uptake of CLTS, and empowering them with increased CLTS knowledge and authority of the program in their chiefdom allowed chiefs to closely monitor village sanitation progress and follow-up with their headmen/headwomen. These key agents of change are important facilitators of public health goals such as the elimination of open defecation in Zambia by 2020.