Background. Blood donation is a novel act to save the lives of people who face serious medical and surgical conditions. Since the demand for blood supply is too high, there is a shortage of blood which causes significant morbidity and mortality. To increase blood supply and maintain adequate quantity of blood, regular and volunteer blood donation practice is needed, which meets the increased demand for blood. Therefore, this systematic review and meta-analysis was aimed at assessing the prevalence of blood donation practices and associated factors in Ethiopia. Method. PubMed/MEDLINE, HINARI, Embase, Scopus, Google Scholar, African Journals Online (AJOL), and published and unpublished articles from the Ethiopian University repository were searched to find articles. Cochrane
I
2 statistics and Egger’s test with funnel plots were done to check heterogeneity and publication bias, respectively. Subgroup analysis by region, study subjects, study setting, and sample size was done due to heterogeneity, as well as sensitivity analysis. Result. Twenty studies from different regions with a total study subject of 8546 were included in the final review. The pooled prevalence of blood donation practice in Ethiopia was 25.82% (95% CI: 21.45-30.19). Having good knowledge of blood donation (
AOR
=
2.85
; 95% CI: 2.33-3.48) and favorable attitude (
AOR
=
4.35
; 95% CI: 2.93-6.45) were factors associated with blood donation practice in Ethiopia. Conclusion. The pooled prevalence of blood donation practices in Ethiopia was short of the demand for blood due to the increase in serious medical conditions and road traffic accidents. Knowledge and attitude towards blood donation were significantly associated with blood donation practice. Therefore, awareness creation and health education programs targeting blood donation practice should be strengthened.