Incarcerated people are at disproportionately high risk of contracting COVID-19. Prisons are epicenters for COVID-19 transmission, including to the community. High rates of preexisting health conditions, limited access to quality health care, and inability to social distance make it impossible to reduce the impact of COVID-19 in prisons. Due to a history of compounded social determinants, incarcerated populations are disproportionately composed of people of color and people with stigmatized behavioral health disorders. Rapid decarceration is needed to promote health equity. Historical mass decarceration events demonstrate feasibility to rapidly release large groups of people while maintaining public safety. Iran and Ireland have released substantial portions of their prison populations by transitioning people to home confinement. In the United States and Uganda, some jurisdictions have reduced new incarcerations through policies that decrease arrests. These policies must be globally expanded to contain the epidemic, and its potential health consequences, while addressing health equity.