Where the Global Health Security Agenda (GHSA) seeks to accelerate progress toward a world safe and secure from public health emergencies, the realization of GHSA ‘Action Packages’ will require national governments to establish necessary legal frameworks to prevent, detect, and respond to infectious disease. By analyzing the scope and content of existing national legislation in each of the GHSA Action Packages, this comparative cross-national research has developed a framework that disaggregates the legal domains necessary to meet each Action Package target. Based upon these legal domains, this study developed an assessment tool that can identify specific attributes of national legislation. This article applies this tool to assess the legal environment in twenty Sub-Saharan African countries, examining the content of laws across the GHSA Action Packages, analyzing the legal domains necessary to implement each Action Package, and highlighting specific national laws that reflect attributes of each legal domain.