Abstract Background Artemisinin-based combination therapy (ACT) and novel drug combinations are available and used in African countries to treat uncomplicated malaria. Network meta-analysis methods are rarely and poorly applied for the comparison of their efficacies. This method was applied on a set of randomized controlled trials to illustrate its usefulness. Methods A literature review available in Pubmed was conducted in July 2016. Eligible studies, conducted in sub-Saharan Africa, published between 2002 and 2016, focused on randomized controlled trials of at least two artemisinin-based combinations to treat uncomplicated malaria in children and adults. Agglomerate data were: the number of PCR-corrected adequate clinical and parasitological response (ACPR) on day 28, used as the primary enDHAPoint in all interventions, the number of participants and the list of treatments. A Bayesian random effect meta-analysis using a binary outcome was the method to compare the efficacy. Ranking measure was used to obtain a hierarchy of the competing interventions. Results In total, 76 articles were included; 13 treatment regimens were involved and tested in 36,001 patients. Using artemether–lumefantrine (AL) as the common comparator for the entire network, 12 relative treatment effects were estimated and indirect comparisons were obtained. Dihydroartemisinin–piperaquine (DHAP) was shown to be more effective than AL (odds ratio [OR] = 1.92; 95% CI 1.30–2.82; 19,163 patients), ASAQ (OR = 1.70; 95% CI 1.10–2.64; 14,433 patients), and amodiaquine–sulfadoxine–pyrimethamine (AQSP): OR = 2.20; 95% CI 1.21–3.96; 8863 patients. Artesunate–amodiaquine (ASAQ) was comparable to AL (OR = 1.11; 95% CI 0.84–1.45; 21,235 patients). No significant difference was found between artesunate and mefloquine (ASMQ) and AL (OR = 1.20; 95% CI = 0.52-2.8; 13,824 participants). According to treatment ranking, among the WHO-recommended ACT medicines, DHAP was shown to be the most efficacious. Conclusions Based on the available evidence, this study demonstrated the superiority of DHAP among currently recommended artemisinin-based combinations. The application of the methods described here may be helpful to gain better understanding of treatment efficacy and improve future decisions. However, more data are needed to allow robust conclusions about the results in comparison with novel drugs. Further surveillance of the efficacy of anti-malarial drugs and clinical trials are needed to closely follow the evolution of the epidemiology of drug-resistant malaria in Africa.