We study the interrelationships between health, residential segregation, and disaster-related material losses (income loss, job loss, economic/property damages) due to the worst ever man-made disaster of its kind, the Deepwater Horizon oil spill (DHOS). Social, economic, and health consequences of the DHOS disaster were assessed in the Survey of Trauma, Resilience, and Opportunity among Neighborhoods in the Gulf, a population-representative study of adults aged 18 years and older living in coastal counties of the Gulf of Mexico in 2016, about 6 years after the disaster. We found that odds of poor/fair health was nearly three times higher among adults who reported DHOS property damage than among those without this material loss using logistic regression models that controlled for individual-level social determinants of health (race/ethnicity, age, gender, marital status, education, household income, and employment) and adjusted for the multilevel structure of the data. Considering alternative measures of residential segregation by race and income (including dissimilarity, exposure, and polarization or concentration at the extremes), only zip code-level income polarization interacted with DHOS material loss to widen inequalities in health. Damage-related health differences were statistically indistinguishable for zip codes with increasingly concentrated affluence, but damage-related health differences widened rapidly with increasingly concentrated disadvantage. At the maximum (1.6 standard deviations below the mean), nearly three-quarters of adults with damages reported poor/fair health versus less than one-third of those with no damages. Our findings suggest that environmental disaster, through disaster-related material loss, both activates and exacerbates existing social and spatial stratification of health.