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Objectives: The aim of this study was to test the hypothesis that ethnic and ethnolinguistic discrimination, and Post‐Traumatic Stress Disorder (PTSD) related to being Indigenous as well as different aspects of acculturative stress, are associated with poorer health and higher levels of depression among the Nahua Indigenous communities. Materials and methods: Our quantitative survey was carried out in four different regions inhabited by the Nahua people in Mexico. Self‐rated health and depression, the symptoms of PTSD, two facets of acculturative stress and ethnolinguistic discrimination were assessed by questionnaires. The data were analyzed using binary logistic regression models. Results: The symptoms of PTSD and acculturative stress experienced in the workplace were significantly associated with a higher risk of poor self‐rated health, adjusted for various socio‐demographic characteristics. Acculturative stress, discouragement of language use, language avoidance and ethnolinguistic discrimination were related to a higher risk of depression and PTSD. Discussion: Our research implies that ethnic and linguistic discrimination, acculturative stress and the memory of harm linked to being Indigenous reflected in the symptoms of PTSD, are important predictors of poorer health and depression among Nahua groups in Mexico. These adverse effects could be significantly counteracted by effective dealing with stigmatization and discrimination against Indigenous people in Mexico and by replacing strong assimilation pressures with integrational approaches that respect ethnolinguistic diversity and reduce socioeconomic marginalization. [ABSTRACT FROM AUTHOR]