Background: In spite of, the need for evidence-based intervention on the potential harmful effects of self-medication practices during pregnancy, there is no systematic review and meta-analysis study regarding self-medication practices in Ethiopia. Therefore, the aim of this study is to determine prevalence of self-medication practice and associated factors among pregnant women in Ethiopia. Method: We used PubMed, the Cochrane Library, Google Scholar, the Wiley Online Library, and African Journals Online to choose important studies. The I-squared statistic method was used to check for heterogeneity between studies. Random effect model was used to estimate the pool prevalence of self-medication among pregnant women. Publication bias was determined by the funnel plot and Egger’s test. Result: A total of 11 studies with 4643 study participants were included in this review. The finding from the current meta-analysis showed that the overall prevalence of self-medication practice among pregnant women is 33.92% (95% CI: 23.15–44.70, I² value = 80.9%). First trimester of pregnancy (OR: 2.24, 95% CI: 1.44–3.47), women who faced health problems during pregnancies at the moment (OR: 5.7, 95% CI: 3.92–8.29), previous self-medication practice (OR: 13.07, 95% CI: 5.14–33.25) and previous pregnancy-related problems (OR: 2.065, 95% CI: 1.44–2.96) were positively associated with self-medication practice among pregnant women. Conclusion: The prevalence of self-medication practices among pregnant women is found to be high. Self-medication practices of the pregnant women were significantly higher among women who were in first-trimester pregnancy, encountered illness during pregnancy, previous self-medication history, and previous pregnancy-related problems. Prospero registration number: CRD42023394907.