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Neonatal sepsis remains one of the most pressing public health challenges in Africa, threatening progress towards the UN Sustainable Development Goal target 3.2 of reducing neonatal mortality to 12 deaths or less per 1000 livebirths. Beyond the well recognised barriers to diagnosis, treatment, and prevention, additional and often overlooked determinants, including sociocultural norms, fragmented health systems, inequities in care, and low political will, continue to stall progress and sustain unacceptably high mortality rates. Antimicrobial-resistant infections further compound this crisis: neonatal sepsis has become a prime example of antimicrobial resistance in Africa, where neonates are at disproportionate risk. Without urgent context-appropriate actions, the region will continue to carry the greatest burden of preventable neonatal deaths. In this Personal View, we assess the growing threat of antimicrobial-resistant neonatal sepsis in Africa, identify priority health-care and health-system gaps, and appraise evidence-based interventions that remain underimplemented. We argue that political inaction and systemic neglect are the central drivers of this crisis and that sustainable progress requires a shift towards a community-centred One Health approach that integrates biomedical, environmental, and sociocultural dimensions of care. Only by uniting global and local leadership and by tailoring strategies to the diverse realities across African countries can progress be accelerated towards ending preventable neonatal deaths and a better future for all.