Background: Tuberculosis (TB) continues to be a public health challenge not only in Rwanda, but also worldwide. Existing literature indicates that TB is one of the most leading causes of death. However, the available evidence indicates a limited understanding of the association between TB and mortality, specifically in Rwanda. Therefore, the aim of this study was to investigate the prevalence, and factors associated with mortality among clinically diagnosed tuberculosis (TB) patients in Rwanda, Method: This study employed a cross-sectional study design, using data from 4,028 TB patients who were clinically diagnosed and registered in the computerized TB case based surveillance system used by health facilities nationwide from July 2019 to June 2022. Multivariate analysis was conducted to determine the adjusted association between TB and mortality, while controlling for confounding factors. Results: Of the total sample, 506 (14.7%) died during treatment. The findings indicate that in the univariate analysis, most variables showed a significant association with TB mortality. For instance, individuals aged 50 and above (COR=2.5, 95% CI=2.10-3.03) and females (COR=1.30, 95% CI=1.09-1.56) were more likely to die. Additionally, having pulmonary tuberculosis (COR=1.21, 95% CI=1.01-1.44), being HIV-positive (COR=1.99, 95% CI=1.46-2.72), or being underweight (COR=1.39, 95% CI=1.14 1.69) showed a higher likelihood of mortality. After controlling for different variables, older age (AOR=2.54, 95% CI=2.10-3.06), underweight (AOR=1.39, 95% CI=1.14 1.69), and HIV-positive status (AOR=2.93, 95% CI=2.59-3.59) remained significantly associated with mortality. Conclusion: This study highlights the high TB mortality rate among TB patients clinically diagnosed in Rwanda compare to the National target, which is 6.5% by the end of 2022. Additionally, the study illustrates the type of pulmonary TB need more attention as well as the patients aged above 50 years, the patients underweight as well as the patient’s HIV positive. These findings could inform public health policies and interventions aimed at reducing mortality rates in TB patients in Rwanda and other similar settings.