Background: In resource-limited settings with a high prevalence of human immunodeficiency virus (HIV) infection such as Zambia, decentralization of HIV/acquired immunodeficiency syndrome (HIV/AIDS) treatment and care with effective use of resources is a cornerstone of universal treatment and care. Objectives: This research aims to analyse the cost effectiveness of the National Mobile Antiretroviral Therapy (ART) Services Programme in Zambia as a means of decentralizing ART services. Methods: Cost-effectiveness analyses were performed using a decision analytic model and Markov model to compare the original ART programme, 'Hospital-based ART', with the intervention programme, Hospital-based plus 'Mobile ART', from the perspective of the district government health office in Zambia. The total cost of ART services, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were examined. Results: The mean annual per-patient costs were 1259.16 USD for the original programme and 2601.02 USD for the intervention programme, while the mean number of QALYs was 6.81 for the original and 7.27 for the intervention programme. The ICER of the intervention programme relative to the original programme was 2965.17 USD/QALY, which was much below the willingness-to-pay (WTP), or three times the GDP per capita (4224 USD), but still over the GDP per capita (1408 USD). In the sensitivity analysis, the ICER of the intervention programme did not substantially change. Conclusion: The National Mobile ART Services Programme in Zambia could be a cost-effective approach to decentralizing ART services into rural areas in Zambia. This programme could be expanded to more districts where it has not yet been introduced to improve access to ART services and the health of people living with HIV (PLHIV) in rural areas.