This study examines links between racial residential segregation and estimated ambient air toxics exposures and their associated cancer risks using modeled concentration estimates from the U.S. Environmental Protection Agency’s National Air Toxics Assessment. We combined pollutant concentration estimates with potencies to calculate cancer risks by census tract for 309 metropolitan areas in the United States. This information was combined with socioeconomic status (SES) measures from the 1990 Census. Estimated cancer risks associated with ambient air toxics were highest in tracts located in metropolitan areas that were highly segregated. Disparities between racial/ethnic groups were also wider in more segregated metropolitan areas. Multivariate modeling showed that, after controlling for tract-level SES measures, increasing segregation amplified the cancer risks associated with ambient air toxics for all racial groups combined [highly segregated areas: relative cancer risk (RCR) = 1.04; 95% confidence interval (CI), 1.01–107; extremely segregated areas: RCR = 1.32; 95% CI, 1.28–1.36]. This segregation effect was strongest for Hispanics (highly segregated areas: RCR = 1.09; 95% CI, 1.01–1.17; extremely segregated areas: RCR = 1.74; 95% CI, 1.61–1.88) and weaker among whites (highly segregated areas: RCR = 1.04; 95% CI, 1.01–1.08; extremely segregated areas: RCR = 1.28; 95% CI, 1.24–1.33), African Americans (highly segregated areas: RCR = 1.09; 95% CI, 0.98–1.21; extremely segregated areas: RCR = 1.38; 95% CI, 1.24–1.53), and Asians (highly segregated areas: RCR = 1.10; 95% CI, 0.97–1.24; extremely segregated areas: RCR = 1.32; 95% CI, 1.16–1.51). Results suggest that disparities associated with ambient air toxics are affected by segregation and that these exposures may have health significance for populations across racial lines.