Background: Tuberculosis (TB) remains one of the leading causes of morbidity and mortality among indigenous peoples in Brazil, and identifying the risk factors for TB in this population secondary to specific epidemiological conditions is essential for recommending interventions aimed at disease control. Methods: This case-control study was conducted with an indigenous population between June 2009 and August 2011 in Dourados, Brazil. Tuberculosis cases reported to the national disease surveillance programme were paired with two control cases matched by age and geographic location. Results: There were 63 cases included in this study, and the annual incidence of TB in the indigenous communities examined was 222 (95% CI, 148–321) per 100 000 inhabitants. The multivariate analysis demonstrated that the variables associated with TB infection included male gender (OR 2.6; 95% CI 1.3–5.3), not owning a home (OR 3.4; 95% CI 1.2–10.1), illiteracy (OR 2.4; 95% CI 1.1–5.0), TB contact (OR 2.4; 95% CI 1.2–4.8) and work performed in a sugar cane factory (OR 6.8; 95% CI 1.2–36.9). Conclusion: There is a potential relationship between exposure to sugar cane manufacturing processes and tuberculosis infection among indigenous populations.