Background Psychiatric disorders, particularly depression is prevalent among patients with tuberculosis (TB) and affect their treatment compliance. Patients with tuberculosis can develop depression due to multiple factors like longer treatment duration, social stigma, lack of family support, etc.In this study, depression and its associated factors were examined among patients with tuberculosis enrolled in a directly observed treatment short-course (DOTS) center in North Delhi. Methods In this DOTS center-based, cross-sectional study, 320 patients with pulmonary and extra-pulmonary TB above 18 years old were included. Basic socio-demographic information was gathered using a Hindi questionnaire, and depression was identified using the patient health questionnaire-9. People who received a score of 10 or higher were deemed to have depression. The Statistical Package for Social Sciences (SPSS) version 21 (IBM Corp., Armonk, NY, USA) was used for data analysis. Analysis between depression and no-depression groups was done by the chi-square test and a p-value< 0.05 was considered statistically significant. Results The study involved 320 patients in all, 193 (60.3%) of whom were men. The median age was 38 years, and the interquartile range (IQR) was 24 to 52 years. Depression was found to be present in half of the patients. Patients with a higher proportion of depression were male, belonged to the middle or below socio-economic status, were currently unemployed and literate, had monthly family income less than 8000 rupees, weight below 45 kg, used alcohol and tobacco, and were undergoing intensive phase (IP) of TB treatment (p-value< 0.05). Depression was not found to be associated with age, site of TB, previous history of anti-tubercular treatment (ATT) intake, marital status, and family size. Conclusion Depression among patients with TB is common and affects half of the patients afflicted with it. When evaluating patients with TB, physicians and DOTS providers should have a high index of suspicion for depression.