OBJECTIVES:  Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of antimalarial agents in the country and we performed a systematic review and meta-analysis on this topic to obtain stronger evidence on treatment outcomes of malaria from the existing literatures in Ethiopia. METHODS: A systematic literature search using the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement was conducted on studies from pubmed, google scholar, and science direct databases to identify published and unpublished literatures. RESULTS:  Twenty-one studies were included in the final analysis with a total number of 3123 study participants. Treatment outcomes were assessed clinically and parasitologically using WHO guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28^th day. Overall, a significant high treatment success of 92.9% (95% CI: 89.1-96.6), p<0.001, I=98.39% was noticed. However, treatment success was higher in P. falciparum malaria patients treated with artemether-lumefantrine than chloroquine for P. vivax patients [98.1% (97.0-99.2), p<0.001, I= 72.55 versus 94.7% (92.6-96.2), p<0.001, I=53.62%]. Seven studies reported the adverse drug reactions to antimalarial treatment; of 822 participants, 344 of them were exposed to adverse drug reactions with a pooled event rate of 39.8% (14.1-65.5), p=0.002. CONCLUSIONS: On the basis of this review, antimalarial treatment success was high (92.9%) and standard regimens showed good efficacy against P. falciparum (98.1%) and P. vivax (94.7%) infections in Ethiopia, but associated with high rates of adverse drug reactions. However, these ADRs were not serious enough to discontinue antimalarial treatment. Our results suggests that the current antimalarial medications are effective and safe, however, greater priority should be placed on the discovery of newer antimalarial drugs to achieve successful outcomes as resistance seems inevitable since cases of antimalarial drug resistance have been reported from other areas of the world.