This qualitative study of task shifting examined tuberculosis (TB) therapy under modified community-based directly observed treatment short-course (CB-DOTS) in Kampala, Uganda. New TB patients selected one of two strategies: home-based DOTS and clinic-based DOTS. Relevant socio-economic characteristics, treatment-seeking experiences and outcomes were assessed over eight months of follow-up. Of 107 patients recruited, 89 (83%) selected home-based DOTS. Sixty-two patients (70%) under home-based DOTS and 16 patients (89%) under clinic-based DOTS had successful outcomes following completion of tuberculosis therapy. Treatment supporters’ provision of social support beyond observing drug ingestion contributed to successful outcomes under both strategies. Home-based DOTS provides continuity of social support during therapy, strengthening the potential for treatment success. Conventional health facility–based DOTS can be modified in resource-limited urban Africa to offer a viable DOTS strategy that is sensitive to personal preference. Shifting the task of DOTS support away from only qualified health workers to include laypersons in the patients’ social-support network may contribute to meeting World Health Organization (WHO) treatment targets. We recommend an intervention evaluating this modified DOTS strategy on a larger scale in TB high-burden, resource-poor urban settings.