Background Aetiological data for neonatal infections are essential to inform policies and programme strategies, but such data are scarce from sub-Saharan Africa. We therefore completed a systematic review and meta-analysis of available data from the African continent since 1980, with a focus on regional differences in aetiology and antimicrobial resistance (AMR) in the past decade (2008-18). Methods We included data for microbiologically confirmed invasive bacterial infection including meningitis and AMR among neonates in sub-Saharan Africa and assessed the quality of scientific reporting according to Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI) checklist. We calculated pooled proportions for reported bacterial isolates and AMR. Findings We included 151 studies comprising data from 84 534 neonates from 26 countries, almost all of which were hospital-based. Of the 82 studies published between 2008 and 2018, insufficient details were reported regarding most STROBE-NI items. Regarding culture positive bacteraemia or sepsis, Staphylococcus aureus, Klebsiella spp, and Escherichia coli accounted for 25% (95% CI 21-29), 21% (16-27), and 10% (8-10) respectively. For meningitis, the predominant identified causes were group B streptococcus 25% (16-33), Streptococcus pneumoniae 17% (9-6), and S aureus 12% (3-25). Resistance to WHO recommended β-lactams was reported in 614 (68%) of 904 cases and resistance to aminoglycosides in 317 (27%) of 1176 cases. Interpretation Hospital-acquired neonatal infections and AMR are a major burden in Africa. More population-based neonatal infection studies and improved routine surveillance are needed to improve clinical care, plan health systems approaches, and address AMR. Future studies should be reported according to standardised reporting guidelines, such as STROBE-NI, to aid comparability and reduce research waste.