Background <p>Malaria remains a significant public health concern in Mozambique. Early diagnosis and the prompt use of effective drugs are essential for malaria control in endemic regions. This review aims to synthesize the existing evidence concerning the efficacy of artemether-lumefantrine (AL) in treating uncomplicated <i>Plasmodium falciparum</i> malaria in Mozambique.</p> Methods <p>This systematic review and meta-analysis include studies evaluating the efficacy of AL using the World Health Organization standard protocol in Mozambique across children under 5&#xa0;years of age and adults, regardless of publication year. The main outcome was efficacy, defined as the proportion of participants who had an adequate clinical and parasitological response, without or with Polymerase Chain Reaction (PCR) correction. Other outcomes included day 3 positivity rate, early treatment failure, late clinical failure and late parasitological failure. Data were obtained from electronic searches of PubMed and ScienceDirect citations. The Rayyan software assessed the adherence of all studies to the stipulated inclusion criteria. The studies' risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Pooled efficacy was calculated based on the per-protocol population. The heterogeneity between studies was assessed using Cochran’s Q statistic, the τ², and the I² statistic, and all statistical analyses were performed using the R software.</p> Results <p>Six studies, comprising 20 single-arm trials and including 1862 participants, were included in the analysis. Studies were conducted across Mozambique and enrolled both children and adults from the country’s three main regions (South, Centre, and North). The pooled uncorrected efficacy of AL was 91.0% (95% CI 84.2–94.6), while the PCR-corrected efficacy was 98.3% (95% CI 96.9–99.1). During the 28-day follow-up period, early treatment failure was observed in 0.05% (95% CI 0.01–0.38) of participants. Late clinical failure and late parasitological failure occurred in 2.73% (95% CI 1.65–4.50) and 5.3% (95% CI 3.10–8.96) of participants, respectively. Recrudescence was observed in 1.8% (95% CI 1.20–2.70) of cases, whereas new infections accounted for 8.6% (95% CI 7.30–10.10). The day 3 parasite positivity rate remained low, at about 0.78% (95% CI 0.21–2.81).</p> Conclusions <p>AL remains efficacious for the treatment of uncomplicated malaria with an efficacy above 90%, and may consequently continue to be used as the first-line treatment option in Mozambique among all vulnerable groups.</p> <p><i>Registration number prospero</i>: 369991.</p>