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Abstract Background The governments of Guinea, Liberia, and Sierra Leone have acknowledged that weak health systems and poor coordination of efforts hampered effectiveness of the 2014–2016 Ebola outbreak response. The bitter experience of the Ebola outbreak response served as an important catalyst for increased efforts to comply with World Health Organization (WHO) International Health Regulations (IHR 2005), Performance of Veterinary Services (PVS) Pathway capacities, and Global Health Security Agenda (GHSA) goals. In November 2016, an interministerial meeting held in Dakar, Senegal, resulted in formalized commitments from the three nations to strengthen resilience to health threats by establishing a Regional Strategic Roadmap to institutionalize the One Health approach. Since then, each country has made significant progress towards establishing National One Health Platforms to coordinate health security interventions, in collaboration with international partners. This paper outlines the methodology and results of these efforts for the period June 2016–January 2019, with a specific focus on activities supported by the US Agency for International Development (USAID)-funded Preparedness & Response (P&R) project. Objectives In support of the West African Health Organization’s November 2016 Regional Strategic Roadmap for institutionalization of the One Health approach, the Preparedness & Response (P&R) project worked in coordination with national partners in Guinea, Liberia, and Sierra Leone to establish multisectoral, One Health coordinating mechanisms. Methodology The global USAID-funded P&R project was launched in 2014 to support the achievement of this objective, and began coordinating with partners in Guinea, Liberia, and Sierra Leone in 2016 to tailor its multi-step conceptual framework to fit the priorities and operating constraints of national stakeholders. Organized in phases of Collaboration (building key relationships), Formalization (defining and establishing a coordination structure), and Implementation (using newfound coordination to produce better health security outcomes), the framework features steps such as One Health sensitizations for multisectoral national stakeholders, development of One Health platform terms of reference and other operating guidelines, and application of these tools to coordination of technical assistance during outbreaks. Results In Guinea, Liberia, and Sierra Leone, in less than 3 yrs there has been a marked improvement in cross-sectoral coordination on health security actions. All three countries have passed legislation establishing permanent multisectoral coordination mechanisms referred to in this document as National One Health Platforms, or simply Platforms; instituted an annual mechanism for assessing capacity and performance of these platforms to lead health security actions; and have undertaken key steps towards developing and updating National Preparedness & Response Plans which truly reflect the multisectoral nature of emerging disease threats. However, multisectoral coordination is a work in progress: government stakeholders and their international partners continue to work together to further strengthen national ownership and investment in the newly established Platforms. Conclusion and next steps Newly established Platforms in Guinea, Liberia, and Sierra Leone offer a long-term structure for coordinating health security actions. However, given the short period of time since their formalization, they depend on continued national, regional, and international resources to build from recent progress and further improve capacity and performance. Regional programs such as the World Bank Regional Disease Surveillance Systems Enhancement (REDISSE) project are of critical importance in keeping the momentum going. The highlighted progress and outputs to date provide reasons and motivation for continued, longer-term investment in the Platforms.