Amid the array of challenges prompted by the COVID-19 pandemic, the policy response of governments proved vital. Different states in the U.S. pursued varied policy approaches that demonstrated distinct divergences in impact. Particularly, contrasting state contexts produced markedly assorted frameworks for the delivery of public health services, which indicate potential effects for COVID-19 policy implementation. Using the rates of COVID-19 vaccination as a measure of policy execution, the purpose of this study is to examine the political and administrative influences contributing to differences in COVID-19 public health policy outcomes among the states in the U.S. Ordinary least squares (OLS) regression models included data sources of nationally representative information pertaining to state public health attributes of politics and administration during the height of the pandemic and vaccine campaign. The findings suggest that state political leadership and fiscal capacity display significant associations with COVID-19 vaccination disparities, while other administrative indicators did not. The results signal important policy implications for the politics–administration dynamic within the COVID-19 pandemic and offer further understanding toward the roles of federalism and governance in future public health emergencies.