Introduction Children and adolescents (0-19 years) living with HIV (CALHIV) in Uganda have historically had lower viral load suppression (VLS) rates than adults and this was partly attributed to sub-optimal antiretroviral therapy (ART) regimens. By June 2019, less than 50% of CALHIV were on optimal regimens despite appropriate policies in place. In July 2019, Ministry of Health (MOH) embarked on an ART optimization campaign to put all CALHIV on optimal regimens. We describe the process, challenges, and achievements during June 2019 – March 2021. Methods The campaign started in July 2019 and ART optimization was phased by age and by region due to ART stock shortage and gradually spread to the entire country with realization of sufficient stock. ART optimization referred to initiating or transitioning CALHIV on either an integrase strand transfer inhibitor(dolutegravir) or a protease inhibitor (Boosted lopinavir) as the anchor drug. Implementation of the campaign involved building capacity for ART optimization for all stakeholders and weekly use of robust data to monitor progress and make timely interventions along with regular supervision and onsite mentorships. MOH developed indicators on optimization which the implementing partners reported at weekly meetings facilitated by the MOH. A data call was made at end of March 2021 to determine the progress on ART optimization of CALHIV in Uganda and VLS analysis was done to assess the early impact of ART optimization. Results Adolescents comprised the majority (40,931/ 64,723; 63.2%) of CALHIV in HIV care by March 2021. Almost all (63,053/64,723; 97.4%) of CALHIV had been transitioned to optimal ART regimens. Despite the successful ART optimization for CALHIV, viral load suppression increased just slightly and remained suboptimal (<95%) by March 2021. Conclusions Proper preparation and timely data use for decision making enabled Uganda to succeed at ART optimization for almost all CALHIV amidst the COVID19 pandemic. However, ART optimization alone was not sufficient to have optimal viral load suppression nationally.