Indigenous peoples around the world face significant health disparities relative to the dominant groups in their countries, yet the magnitude and patterns of health disparities vary across countries. We use data from the National Health Interview Survey and Mexican Family Life Survey to examine the health of Indigenous peoples in Mexico and American Indians and Alaska Natives in the USA and to evaluate how they fare relative to the majority populations in their countries (non-Indigenous Mexicans and non-Hispanic Whites, respectively). We assess disparities in self-rated health and activity limitations, with a focus on how Indigenous health disparities intersect with educational gradients in health. Regression analyses reveal three primary findings. First, Indigenous health disparities are larger in the USA than in Mexico. Second, differences in educational attainment account for most of the differences between Indigenous and non-Indigenous populations in Mexico, but less than half in the USA. Third, in both countries, health is moderated by educational attainment such that between-group disparities are largest at the highest levels of education. However, for Indigenous Mexicans there is a “cross-over” in which Indigenous Mexicans report better health at the lowest level of education. Overall, this study finds a weak relationship between education and Indigenous health, and raises the question about the validity of using traditional measures of SES in Indigenous contexts.