Background Over the past several decades, rural and indigenous populations in Latin America have experienced abrupt and profound transformations in their lifestyles and economies, many having remarkable health consequences. Yet, these changes have had heterogeneous effects on the population's biology in different local contexts. Objectives The primary goal was to characterize the nutrition transition and biomarkers of noncommunicable diseases (NCD) risk in 2 Chilean indigenous populations that have had divergent histories of subsistence strategies (agropastoralism compared with hunter-gathering) in the last few millennia and live in contrasting environments, and to identify context-specific factors driving the nutrition and epidemiological transitions. Methods One-hundred-and-ninety (90 Pehuenche and 100 Atacameño) participants aged 18–87 y completed demographic, food-frequency, and physical activity questionnaires as well as measurements of some NCD risk biomarkers: blood pressure, weight, height, body fat percentage, waist circumference, blood total cholesterol, HDL cholesterol, triglycerides, and glucose. Framingham risk scores (FRSs) were calculated based on age, sex, total cholesterol, HDL cholesterol, systolic blood pressure, smoking, diabetes status, and hypertension medication. Results Few differences in dietary composition and physical activity patterns were observed between the 2 populations. Multivariate analyses showed no differences between the 2 populations in any of the individual NCD risk biomarkers or FRSs after adjusting for age, sex, time since last meal, food insecurity in childhood, ultraprocessed food consumption, and physical activity. Conclusions Despite contrasting ecological and historical contexts, the 2 groups are converging into similar processes of market and wage-labor integration and transitioning to a Western diet high in processed and nonlocal foods, although some aspects of their “traditional” foodways are still in practice. The frequency of individuals exhibiting NCD biomarkers “at-risk” is relatively high and corresponds to other populations that have gone through nutrition transition. Furthermore, none of these biomarkers or FRSs differed between the 2 populations, suggesting a homogenization in the NCD risk factors., Over the past few decades, indigenous populations in Latin America have experienced major transformations in their lifestyles and economies, resulting in far-reaching consequences for their health and well-being. In this study, several biomarkers for non-communicable diseases (NCD) related to metabolic syndrome were evaluated among two indigenous populations living in highly contrasting environments (Atacama Desert and temperate rainforests in the Andes mountain slopes) who have had divergent histories of subsistence strategies (agropastoralism and hunting-gathering). Context-specific factors driving the nutrition transition in each group were identified; but, despite variation in local contexts, their diets and lifestyles are converging into similar patterns. Likewise, no significant differences in NCD risk for any of the biomarkers evaluated were found, suggesting a homogenization in the health outcomes associated with food and lifestyle changes in this region.