We investigated the distribution of comorbidities among adult tuberculosis (TB) patients in Chiapas, the poorest Mexican state, with a high presence of indigenous population, and a corridor for migrants from Latin America. Secondary analysis on 5508 new adult TB patients diagnosed between 2010 and 2014 revealed that the most prevalent comorbidities were diabetes mellitus (DM; 19.1%) and undernutrition (14.4%). The prevalence of DM in these TB patients was significantly higher among middle aged (41–64 years) compared with older adults (⩾65 years) (38.6% vs. 23.2%; P < 0.0001). The prevalence of undernutrition was lower among those with DM, and higher in communities with high indigenous presence. Immigrants only comprised 2% of all TB cases, but were more likely to have unfavourable TB treatment outcomes (treatment failure, death and default) when compared with those born in Chiapas (29.5% vs. 11.1%; P < 0.05). Unfavourable TB outcomes were also more prevalent among the TB patients with undernutrition, HIV or older age, but not DM (P < 0.05). Our study in Chiapas illustrates the challenges of other regions worldwide where social (e.g. indigenous origin, poverty, migration) and host factors (DM, undernutrition, HIV, older age) are associated with TB. Further understanding of these critical factors will guide local policy makers and health providers to improve TB management.