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Objectives Global antimicrobial resistance (AMR) surveillance in Neisseria gonorrhoeae is essential. In 2017–18, only five (10.6%) countries in the WHO African Region reported to the WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP). Genomics enhances our understanding of gonococcal populations nationally and internationally, including AMR strain transmission; however, genomic studies from Africa are extremely scarce. We describe the gonococcal genomic lineages/sublineages, including AMR determinants, and baseline genomic diversity among strains in Uganda, Malawi and South Africa, 2015–20, and compare with sequences from Kenya and Burkina Faso. Methods Gonococcal isolates cultured in Uganda (n  = 433), Malawi (n  = 154) and South Africa (n  = 99) in 2015–20 were genome-sequenced. MICs were determined using ETEST. Sequences of isolates from Kenya (n  = 159), Burkina Faso (n  = 52) and the 2016 WHO reference strains (n  = 14) were included in the analysis. Results Resistance to ciprofloxacin was high in all countries (57.1%–100%). All isolates were susceptible to ceftriaxone, cefixime and spectinomycin, and 99.9% were susceptible to azithromycin. AMR determinants for ciprofloxacin, benzylpenicillin and tetracycline were common, but rare for cephalosporins and azithromycin. Most isolates belonged to the more antimicrobial-susceptible lineage B (n  = 780) compared with the AMR lineage A (n  = 141), and limited geographical phylogenomic signal was observed. Conclusions We report the first multi-country gonococcal genomic comparison from Africa, which will support the WHO GASP and WHO enhanced GASP (EGASP). The high prevalence of resistance to ciprofloxacin (and empirical use continues), tetracycline and benzylpenicillin, and the emerging resistance determinants for azithromycin show it is imperative to strengthen the gonococcal AMR surveillance, ideally including genomics, in African countries. [ABSTRACT FROM AUTHOR]