OBJECTIVES: To estimate the prevalence of sickle cell trait, sickle cell disease, beta-thalassaemia minor and beta-thalassaemia major among Odisha's indigenous populations and to examine associated haematological profiles and survival outcomes based on socioeconomic factors. DESIGN: A population-based cross-sectional study. SETTING: Fourteen tribal-dominated districts of Odisha, eastern India PARTICIPANTS: A total of 8774 tribal individuals aged 11 months to 99 years, selected using multistage cluster sampling from 9711 households. PRIMARY AND SECONDARY OUTCOME: Primary outcomes were the prevalence of sickle cell trait, sickle cell disease, beta-thalassaemia minor and beta-thalassaemia major. Secondary outcomes included haemoglobin levels, serum iron, unsaturated iron-binding capacity, awareness regarding the diseases, nutritional status and estimated survival by sex and wealth quintile. RESULTS: The prevalence of sickle cell trait was 5.20%, sickle cell disease 0.40%, beta-thalassaemia minor 4.18%, and beta-thalassaemia major 0.44%. Females had slightly higher traits and minor prevalence, while the disease was more common in males; however, these differences are not statistically significant. Median serum iron levels were higher among individuals with β-thalassaemia major, while individuals with sickle cell disease exhibited consistently lower haemoglobin levels. Awareness was critically low (15.28%). Nutritional status and survival differed by condition, sex and wealth. Median survival was lowest for sickle cell disease and among the poorest, highlighting the need for targeted screening and education. CONCLUSION: This study highlights the substantial burden of haemoglobinopathies and significant health disparities among the Indigenous populations of Odisha. Expanding screening initiatives, enhancing health education and integrating haemoglobinopathy management into primary healthcare services are crucial for reducing disease burden and improving survival outcomes.