Treatment for tuberculosis lasts for a minimum of 6 months. The treatment burden experienced by patients in a low-incidence setting where directly observed therapy is the standard of care is not well-known. Patients receiving tuberculosis treatment through the chest clinic at a tertiary hospital in Sydney, Australia, participated in a semi-structured interview. The interviews explored the treatment burden experienced by patients and possible solutions to ameliorate this burden. Interviews were conducted until data saturation was achieved. They were recorded, transcribed and analysed using NVivo 12 software. Twenty participants (80% male, mean age 40 years) with pulmonary (n = 13) and extra-pulmonary (n = 7) tuberculosis were interviewed. Participants experienced healthcare, financial, social and medication burdens along with lifestyle changes due to treatment. Medication intake was challenging due to the high number of pills, and 55% (n = 11) of patients experienced fatigue amongst other side effects. Patients found clinic-based directly observed therapy inconvenient, especially those working and/or studying. Suggestions to lessen treatment burden included reducing medication burden and better access to health services. Tuberculosis treatment is associated with substantial treatment burden for patients. Measures to reduce treatment burden including alternative treatment delivery methods which are more accommodating to patients than clinic-based directly observed therapy, such as video directly observed therapy or partially self -administered treatment, should be considered on a case-by-case basis.