Adolescents in resource-constrained environments face increasing sedentary lifestyles and obesity rates, necessitating effective interventions for promoting physical activity and combating non-communicable diseases. This study evaluates the impact of a 12 week Nyakaza Move-for-Health intervention on physical activity, anthropometry, cardiorespiratory fitness, and behaviour change among adolescents in KwaZulu-Natal, South Africa. One hundred twenty-eight adolescents participated, with assessments including self-reported physical activity, anthropometric indices, and cardiorespiratory fitness measures. The intervention significantly increased physical activity levels. The treatment group’s mean score was 2.2 (0.4) at baseline and 2.6 (0.4) (F (14, 79) = 4.884, p = <0.001, η2 = 0.156) at the endline. The body mass index decreased (mean = 22.4 (4.6) at baseline and 21.9 (4.2) at endline; p = 0.025, partial eta squared = 0.025, η2 = 0.004). The intervention programme significantly affected the WHR (mean = 0.80 (0.10) at baseline and 0.76 (0.9) at endline; p < 0.001, partial eta squared = 0.327, η2 = 0.100) and the predicted maximal oxygen uptake (VO2 max) for the treatment group (mean = 42.4 (8.7) at baseline and mean = 43.6 (8.7) at endline; p < 0.711, partial eta squared = 0.017, η2 = 0.033). Focus group discussions indicated shifts in knowledge, attitudes, and motivation towards physical activity. Power analysis revealed strong observed power (PA: 0.983, BMI: 0.098, WHR: 0.887), indicating the robustness of the intervention’s effects. These findings underscore the effectiveness of the intervention in improving physical health outcomes. It is recommended that longitudinal studies be conducted to assess the long-term sustainability and impact of such interventions on adolescents’ health outcomes, thereby informing the development of comprehensive public health policies and programmes to promote physical activity and combat non-communicable diseases in similar settings.