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Introduction: Infant HIV prophylaxis with broadly neutralizing anti‐HIV antibodies (bNAbs) could provide long‐acting protection against vertical transmission. We sought to estimate the potential clinical impact and cost‐effectiveness of hypothetical bNAb prophylaxis programmes for children known to be HIV exposed at birth in three sub‐Saharan African settings. Methods: We conducted a cost‐effectiveness analysis using the CEPAC‐Pediatric model, simulating cohorts of infants from birth through death in Côte d'Ivoire, South Africa and Zimbabwe. These settings were selected to reflect a broad range of HIV care cascade characteristics, antenatal HIV prevalence and budgetary constraints. We modelled strategies targeting bNAbs to only WHO‐designated "high‐risk" HIV‐exposed infants (HR‐HIVE) or to all HIV‐exposed infants (HIVE). We compared four prophylaxis approaches within each target population: standard of care oral antiretroviral prophylaxis (SOC), and SOC plus bNAbs at birth (1‐dose), at birth and 3 months (2‐doses), or every 3 months throughout breastfeeding (Extended). Base‐case model inputs included bNAb efficacy (60%/dose), effect duration (3 months/dose) and costs ($60/dose), based on published literature. Outcomes included paediatric HIV incidence and incremental cost‐effectiveness ratios (ICERs) calculated from discounted life expectancy and lifetime HIV‐related costs. Results: The model projects that bNAbs would reduce absolute infant HIV incidence by 0.3–2.2% (9.6–34.9% relative reduction), varying by country, prophylaxis approach and target population. In all three settings, HR‐HIVE–1‐dose would be cost‐saving compared to SOC. Using a 50% GDP per capita ICER threshold, HIVE‐Extended would be cost‐effective in all three settings with ICERs of $497/YLS in Côte d'Ivoire, $464/YLS in South Africa and $455/YLS in Zimbabwe. In all three settings, bNAb strategies would remain cost‐effective at costs up to $200/dose if efficacy is ≥30%. If the bNAb effect duration were reduced to 1 month, the cost‐effective strategy would become HR‐HIVE–1‐dose in Côte d'Ivoire and Zimbabwe and HR‐HIVE–2‐doses in South Africa. Findings regarding the cost‐effectiveness of bNAb implementation strategies remained robust in sensitivity analyses regarding breastfeeding duration, maternal engagement in postpartum care, early infant diagnosis uptake and antiretroviral treatment costs. Conclusions: At current efficacy and cost estimates, bNAb prophylaxis for HIV‐exposed children in sub‐Saharan African settings would be a cost‐effective intervention to reduce vertical HIV transmission. [ABSTRACT FROM AUTHOR]