Abstract Background Regular monitoring of anti-malarial drug efficacy is vital for establishing rational malaria treatment guidelines and ensuring adequate treatment outcomes. This study aimed to synthesize the available evidence on the efficacy of artemether–lumefantrine for the management of uncomplicated falciparum malaria in Ethiopia. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Relevant published studies were searched from the databases (PubMed, Google Scholar and Clinical trial registry) on published artemether–lumefantrine therapeutic efficacy studies conducted in Ethiopia from 2004 to 2020. The retrieved studies were assessed for quality using the modified Newcastle Ottawa Scale for observational studies and modified Jadad scale for interventional studies. Risk of bias was also assessed by using ROBINS-I tool. OpenMeta-Analyst software was used for the statistical analysis. The review protocol is registered in PROSPERO, number CRD42020201859. Results Fifteen studies (1523 participants) were included in the final analysis. The overall PCR-uncorrected pooled proportion of treatment success of artemether–lumefantrine therapy for uncomplicated falciparum malaria was 98.4% (95%CI 97.6–99.1). A random-effects model was used because of considerable heterogeneity [χ2 = 20.48, df (14), P = 0.011 and I2 = 31.65]. PCR-corrected pooled proportion of treatment success of artemether–lumefantrine therapy was 98.7% (95% CI 97.7–99.6). A random-effects model was used [χ2 = 7.37, df(6), P = 0.287 and I2 = 18.69]. Most studies included in the present review achieved a rapid reduction of fevers and parasitaemia between D0 and D3 of assessment. Adverse events were mostly mild and only two cases were reported as serious, but were not directly attributed to the drug. Conclusion The present meta-analysis suggests that artemether–lumefantrine therapy is efficacious and safe in treating uncomplicated falciparum malaria in Ethiopia. However, owing to the high risk of bias in the included studies, strong conclusions cannot be drawn. Further high-quality RCTs assessing anti-malarial efficacy and safety should be performed to demonstrates strong evidence of changes in parasite sensitivity to artemether–lumefantrine in Ethiopia.