Background Neonatal hyperbilirubinemia is a common clinical problem encountered during the neonatal period, especially in the first week of life. Available clinical guidelines note that early detection and intervention of infants at risk of severe hyperbilirubinemia can facilitate timely and effective prevention of the associated complications. Methods The international databases, PubMed/MEDLINE, EMBASE, CINAHL, Google Scholar, Science Direct, and Cochrane Library, and unpublished reports were systematically searched. Two authors independently extracted all necessary data using a standardized data extraction format. STATA 14 statistical software was employed to analyze the data. The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity between the studies. A random-effect model was computed to estimate the pooled prevalence of pathological neonatal hyperbilirubinemia in Ethiopia. Determinants of neonatal hyperbilirubinemia were analyzed. Results Ten studies fulfilled the inclusion criteria and were included in the meta-analysis. The I2 test result showed high heterogeneity (I2, 98.3%, P = <.001). Using the random effect analysis, the pooled prevalence of neonatal hyperbilirubinemia in Ethiopia was 35.90% (95% confidence interval [CI] [23.79, 48.01]). The results from these studies revealed that the occurrence of pathological neonatal hyperbilirubinemia was significantly associated with the presence of ABO blood incompatibility, Rh isoimmunization, neonatal sepsis (odds ratio [OR]: 4.44; CI: 1.72,11.46), birth asphyxia (OR:1.74; CI: 1.08,2.80), low birth weight (OR: 2.22; CI: 1.46,3.31), and prolonged labor (OR: 3.24; CI: 1.05,10.0). Conclusion The burden of neonatal hyperbilirubinemia is higher in our country as compared with others. ABO blood incompatibility, Rh isoimmunization, neonatal sepsis, birth asphyxia, low birth weight, and prolonged labor were significantly associated with neonatal hyperbilirubinemia.