Under Review. We still lack a unifying theoretical framework—complete with parsimonious empirical tools—to describe interconnected, spatialized, racialized inequalities in the US, a framework that synthesizes socioeconomic and environmental relations and emphasizes mechanisms amenable to policy change. Common quantitative indices tend to be atheoretical, lack explicit causal accounts, and cannot offer policy guidance. In this study, we propose the eco-apartheid framework and index to fill this gap. We develop our index in dialogue with two research traditions with complimentary strengths—American apartheid/redlining and environmental justice mapping. Our index is consistent with those frameworks’ historical, causal narratives, and clarifies the role of structural racism in contemporary U.S. inequalities. In keeping with a South African apartheid analogy, we place greater emphasis on state violence and labor market inequalities than many analogies to apartheid. By aggregating just 6 measures—covering political economy, state violence, and socio-environmental exposures—each amenable to direct policy action, the eco-apartheid index predicts life expectancy differences of over 5 years between census tracts at the top vs. bottom of the index, in the 20 largest US metropolitan areas. It predicts 2 to 3 times higher Covid mortality rates between top vs. bottom zip codes in New York, Los Angeles, and Chicago, in the period before vaccination. The index predicts neighborhood life expectancy better than maps of redlining and air toxin exposure. It performs as well as the Area Depravation and Social Vulnerability indices, with far fewer variables, stronger theory, and clearer policy implications. By demonstrating the empirical validity of the eco-apartheid theoretical framework, we hope to spark research and debate on the spatial intersections of racialized, environmental, and economic inequalities in the United States and around the world.