Recent research shows a significant link between race-ethnicity and income concentration and premature death rates in the U.S. However, most studies focus on Black-White residential concentration, overlooking racial-ethnic diversity. Our study examines the impact of racial-ethnic majority composition on mortality and how this relationship varies across different levels of economic concentration in neighborhoods, as defined by census tracts. Premature death rates (under 65 years of age) were retrieved from abridged period life tables from 67,140 U.S. census tracts derived from the U.S. Small-area Life Expectancy Project. Covariate factors were retrieved from the 2011–2015 American Community Survey (ACS) 5-year estimates. We measured racial-ethnic concentration by grouping neighborhoods using each tract’s majority racial-ethnic group, and approximated income concentration using the Index of Concentration of the Extremes. We used three-level random intercept models to examine the interaction of racial-ethnic and income concentration and its association with neighborhood mortality risk, accounting for covariates. Our study yielded three salient findings. First, mortality risk varied greatly in poor neighborhoods with different racial-ethnic compositions compared to affluent neighborhoods, with notable higher risk in Black-majority areas. Second, in diverse neighborhoods where no single ethnic group forms a majority—referred to as Minority-majority neighborhoods—the mortality risk is comparable to that in White-majority neighborhoods. Third, Hispanic/Latino- and Asian-majority neighborhoods had lower mortality risk than White-majority neighborhoods in areas with a high concentration of poverty, but similar mortality risk in affluent areas. The study suggests that racial-ethnic and socioeconomic area-based measures are important to consider together to address mortality inequities accurately.