Structural racism is a root cause of poor health in the United States and underlies COVID-19-related disparities for Black and Latinx populations. We describe how one community-based organization responded to structural racism and COVID-19 in Florida. Informed by the literature on how public health practice changed from emphasizing prevention (Public Health 1.0) to collaboration between governmental and public health agencies (Public Health 2.0) and examining social determinants of health (Public Health 3.0), we call for a politically engaged Public Health 4.0. (Am J Public Health. 2021;111(S3):S201-S203. https://doi.org/10.2105/AJPH.2021.306408).