Long-standing cultural, economic, and political relationships among Benin, Nigeria, and Togo contribute to the complexity of their cross-border connectivity. The associated human movement increases the risk of international spread of communicable disease. The Benin and Togo ministries of health and the Nigeria Centre for Disease Control, in collaboration with the Abidjan Lagos Corridor Organization (a 5-country intergovernmental organization) and the US Centers for Disease Control and Prevention, sought to minimize the risk of cross-border outbreaks by defining and implementing procedures for binational and multinational public health collaboration. Through 2 multinational meetings, regular district-level binational meetings, and fieldwork to characterize population movement and connectivity patterns, the countries improved cross-border public health coordination. Across 3 sequential cross-border Lassa fever outbreaks identified in Benin or Togo between February 2017 and March 2019, the 3 countries improved their collection and sharing of patients' cross-border travel histories, shortened the time between case identification and cross-border information sharing, and streamlined multinational coordination during response efforts. Notably, they refined collaborative efforts using lessons learned from the January to March 2018 Benin outbreak, which had a 100% case fatality rate among the 5 laboratory-confirmed cases, 3 of whom migrated from Nigeria across porous borders when ill. Aligning countries' expectations for sharing public health information would assist in reducing the international spread of communicable diseases by facilitating coordinated preparedness and responses strategies. Additionally, these binational and multinational strategies could be made more effective by tailoring them to the unique cultural connections and population movement patterns in the region.