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Abstract Background The Karamoja subregion in north-eastern Uganda has very high Tuberculosis (TB)case notification rates and, until recently, had suboptimal treatment completion rates among patients diagnosed with TB. We evaluated community knowledge, attitudes and practices towards Tuberculosis in order to identify barriers to TB control in this region. Methods From September to October 2022, we conducted a community-based survey in four districts in the Karamoja subregion. We collected data on TB knowledge, attitudes, and practices using a structured electronic questionnaire. We generated knowledge, attitude and practice scores. We used a survey-weighted zero-truncated modified Poisson model to assess the association between knowledge/attitude scores and respondents’ characteristics and a complementary log-log model to assess the association between practice scores and respondents’ characteristics. Data analysis was carried out using STATA version 14. Results A total of 1927 respondents were interviewed. Of these, 55.5% were female, and 1320 (68.6%) had no formal education. Overall, 68.5% 95% CI (59.6–76.7%) had knowledge scores of ≥ 60%. Higher TB knowledge scores were associated with being employed (adjusted prevalence ratio, aPR = 1.22, 95% CI 1.04–1.42, p = 0.01) while being a wife in a household was associated with lower TB knowledge (aPR = 0.90, 95% CI 0.82–0.99, p = 0.03). Being 25–34 years old was associated with a positive attitude towards TB (PR = 1.06, 1.01–1.11, p = 0.01). Over 85% of respondents would go to the health facility immediately if they had TB signs and symptoms. Almost all respondents (98.6%) would start TB treatment immediately if diagnosed with the disease. Conclusion More than two thirds of patients had good knowledge and practices towards TB which can be leveraged to improve uptake of TB control interventions in the region. Additional interventions to improve TB knowledge and practice should focus on specific segments within the communities e.g., older women in the households.