BACKGROUND: The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. METHODS: We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts. RESULTS: Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable. CONCLUSION: Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.