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Background: Depression and anxiety are prevalent comorbidities and a major concern for patients with tuberculosis. They are associated with low quality-of-life, poor treatment adherence and increased risk of mortality and morbidity. Aim: To assess the prevalence of depression and anxiety and their predictors among pulmonary tuberculosis patients in Tigray, Northern Ethiopia. Methods: Between January and April 2025, we interviewed 360 patients aged ≥ 18 years, who were confirmed to have pulmonary tuberculosis and had been receiving treatment and follow-up for at least 2 weeks in 10 outpatient tuberculosis clinics in Tigray, Ethiopia. We used the Patient Health Questionnaire 9 and Generalized Anxiety Disorder 7 for data collection, and used SPSS version 29 to analyse the data. Binary logistic regression model was used to identify the predictors of depression and anxiety. Results: P revalence of depression among the patients was 56.7% while prevalence of anxiety was 54.2%. Multivariable regression analysis revealed that smoking, alcohol consumption, adverse drug effects, and perceived stigma were significant risk factors for depression, while treatment support was a protective factor. Smoking, adverse drug effects, HIV/AIDS coinfection, and perceived stigma were significant risk factors for anxiety. Conclusion: The prevalence of depression and anxiety among patients with pulmonary tuberculosis in this study was significantly higher than in other studies. Therefore, there is a need to encourage tuberculosis patients with the identified risk factors to undergo screening for depression and anxiety and to incorporate psychological interventions into their treatment plan.