Abstract Background Tuberculosis (TB) is a communicable disease remains a major global health problem and the leading cause of death from a single infectious agent. Even though many of the WHO recommended TB control strategies were implemented; there is still a major gap in TB case detection and treatment. This study aimed to determine the prevalence of Mycobacterium tuberculosis among presumptive TB patients in Gedeo Zone, Southern Ethiopia. Methods A cross-sectional study was conducted on 384 TB suspected patients in Gedeo Zone from February to July 2021. Data were collected using a pretested structured questionnaire. Laboratory examination was processed using Xpert-MTB/RIF assay. Data entry was made using Epi info version 7 and analyzed by SPSS version 24. Logistic regression models were used to determine the risk factors. Results Out of 384 study participants suspected with TB, M. tuberculosis was isolated from 103 giving an overall prevalence of 26.8%. Males (AOR) = 1.95; 95% CI 1.56–2.65, P = 0.01) were more likely to develop TB than females. Study participants who were illiterate (AOR 2.10; 95% CI 1.17–2.51, P = 0.014) were more likely to develop TB than the educated ones. Cigarette smokers (AOR 2.89; 95% CI 2.10–3.84, P = 0.01), khat chewers (AOR 2.86; 95% CI 1.28–3.79, P = 0.01), vaccination (AOR 0.52; 95% CI 0.21–0.88, P = 0.02), close contact (AOR 3.42; 95% CI 2.24–4.50, P = 0.01) and being positive for HIV (AOR 2.01; 95% CI 1.07–3.52, 0.01) were more likely to develop TB. Conclusion Despite implementation of national and international TB control strategies, TB still remains one of the major public health problems in the country especially in the study area. The high prevalence of MTB was reported different risk groups. Early case detection and management of TB should be given special attention to strengthen and an appropriate control and prevention methods to reduce the emergence and increasing of MTB cases.
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