Background Previous studies on menstrual hygiene practice were largely inconsistent and single national evidence is required. Thus, this study aimed to assess the pooled prevalence of menstrual hygiene and its association with knowledge about menstrual hygiene among female adolescents in Ethiopia. Methods The study was designed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-2015 Guidelines). This systematic review included studies conducted on female adolescents in Ethiopia irrespective of their publication and study period until the end of July 1, 2020. The data extracted in the Microsoft Excel sheet format was exported into the STATA/SE14 version statistical software for further analysis. I.sup.2 test was used to test heterogeneity and publication bias was assessed by using Egger's weighted regression test. Results Thirteen full-text articles including 6907 participants were included in this systematic review and meta-analysis. Using the random effect model, the pooled prevalence of poor menstrual hygiene practice was 48.98% [95% CI: (36.42, 61.53)]. Those female adolescents who had poor knowledge were 2.6 times more likely to have poor menstrual hygiene practice as compared to counterparts [AOR = 2.61, 95% CI: (1.45, 4.72)]. Conclusions The prevalence of poor menstrual hygiene practice was high and knowledge regarding menstrual hygiene was significantly associated with poor menstrual hygiene practice. Information education communication and behavioral change communication at all levels of education should be the primary focus area of the government.