Newborn resuscitation is a medical intervention to support the establishment of breathing and circulation in the immediate intrauterine life. It takes the lion's share in reducing neonatal mortality and impairments. Healthcare providers' knowledge and skills are the key determinants of the success of newborn resuscitation. Many primary studies have been conducted in various countries to examine the level of knowledge and skills of newborn resuscitation and associated factors among healthcare providers. However, these studies had great discrepancies and inconsistent results across East Africa. Hence, this review aimed to synthesize the pooled level of knowledge and skills of newborn resuscitation and associated factors among healthcare providers in East Africa. Studies were systematically searched from February 11, 2023, to March 10, 2023, using PubMed, Google Scholar, HINARI, and grey literature. The effect size measurement of knowledge and skill of health care newborn resuscitation was estimated using the Random Effect Model. The data were extracted by Excel and analyzed using Stata 17 software. The Cochran's Q test and I2 statistic were used to assess the heterogeneity of studies. The symmetry of the funnel plot and Egger's test were used to check for publication bias. A subgroup analysis was done on the study years, sample sizes, and geographical location. Percentages and odds ratios (OR) with 95% CI were used to pool the effect measure. In this systematic review and meta-analysis, a total of 1953 articles were retrieved from various databases and registers. Finally, 17 studies with 7655 participants were included. The overall levels of knowledge and skills of healthcare providers on newborn resuscitation were 58.74% (95% CI: 44.34%, 73.14%) and 46.20% (95% CI: 25.16%, 67.24%), respectively. Newborn resuscitation training (OR = 3.95, 95% CI: 2.82, 5.56) and the availability of newborn resuscitation guidelines (OR = 2.71, 95% CI: 1.90, 3.86) were factors significantly associated with knowledge of health care professionals on newborn resuscitation. Work experience (OR = 5.92, 95% CI, 2.10, 16.70), newborn resuscitation training (OR = 2.83, 95% CI, 1.8, 4.45), knowledge (OR = 3.05, 95% CI, 1.78, 5.30), and the availability of newborn resuscitation equipment (OR = 4.92, 95% CI, 2.80, 8.62) were determinant factors of skills of health care professionals on newborn resuscitation. The knowledge and skills of healthcare providers on newborn resuscitation in East Africa were not adequate. Newborn resuscitation training and the availability of resuscitation guidelines were determinant factors of knowledge, whereas work experience, knowledge, and the availability of newborn resuscitation equipment and training were associated with the skills of healthcare providers in newborn resuscitation. Newborn resuscitation training, resuscitation guidelines and equipment availability, and work experience are recommended to improve healthcare providers' knowledge and skills.