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Abstract Background The emergence and rapid spread of gram-negative bacteria resistant to carbapenems among newborns is concerning on a global scale. Nonetheless, the pooled estimate of gram-negative bacteria resistant to carbapenem that cause neonatal sepsis in developing nations remains unknown. Thus, this study aimed to determine the combined prevalence of gram-negative bacteria resistant to carbapenem in African newborns who were suspected of having sepsis. Methods All studies published from January 1, 2010, up to December 30, 2023, from PubMed, Science Direct, Scopus electronic databases, and the Google Scholar search engine were researched. Isolates tested for carbapenem from neonates with sepsis, English language papers conducted in Africa, and cross-sectional and cohort studies papers were included. Using PRISMA guidelines, we systematically reviewed and meta-analyzed studies that assessed the prevalence of carbapenem-resistant gram-negative bacteria. The “Joanna Briggs Institute” was used critically to evaluate the quality of the included studies. The data analysis was carried out using STATA™ version 17. Heterogeneity across the studies was evaluated using Q and I 2 tests. The subgroup analysis was done and, funnel plot and Egger’s regression test were used to detect publication bias. A sensitivity analysis was conducted. Results All 36 studies were included in the meta-analysis and systematic review. The pooled prevalence of carbapenem resistance in Africa was 30.34% (95% CI 22.03–38.64%). The pooled estimate of gram-negative bacteria resistant to imipenem, and meropenem was 35.57% (95% CI 0.67–70.54%) and 34.35% (95% CI 20.04% – 48.67%), respectively. A. baumannii and Pseudomonas spp. had pooled prevalence of 45.9% (95% CI 33.1–58.7%) and 43.0% (95% CI 23.0–62.4%), respectively. Similarly, Pseudomonas spp. and A. baumannii also exhibited strong meropenem resistance, with a pooled prevalence of 29.2% (95% CI 4.8–53.5%) and 36.7% (95% CI 20.1–53.3%), respectively. E. coli and K. pneumoniae were the two most common isolates. Conclusion There should be urgent antimicrobial stewardship practices, strengthened surveillance systems and effective treatment for neonates with sepsis. There was remarkable variation in resistance across the continent.