We draw on new and original data to examine both partisan and systemic inequities that have fueled the spread of COVID-19 in Native America. We show how continued political marginalization of Native Americans has compounded longstanding inequalities and endangered the lives of Native peoples. Native nations have experienced disproportionate effects from prior health epidemics and pandemics, and in 2020, Native communities have seen greater rates of infection, hospitalization, and death from COVID-19. We find that Native nations have more COVID-19 cases if they are located in states with a higher ratio of Trump supporters and reside in states with Republican governors. Where there is longstanding marginalization, measured by lack of clean water on tribal lands and health information in Native languages, we find more COVID-19 cases. Federal law enables non-members to flout tribal health regulations while on tribal lands, and correspondingly, we find that COVID-19 cases rise when non-members travel onto tribal lands. Our findings engage the literatures on Native American politics, health policy within U.S. federalism, and structural health inequalities, and should be of interest to both scholars and practitioners interested in understanding COVID-19 outcomes across Tribes in the United States.