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The COVID-19 pandemic has ushered in high-throughput sequencing technology as an essential public health tool. Scaling up and operationalizing genomics in Africa is crucial as enhanced capacity for genome sequencing could address key health problems relevant to African populations. High-quality genomics research can be leveraged to improve diagnosis, understand the aetiology of unexplained illnesses, improve surveillance of infectious diseases and inform efficient control and therapeutic methods of known, rare and emerging infectious diseases. Achieving these within Africa requires strong commitment from stakeholders. A roadmap is needed to guide training of scientists, infrastructural development, research funding, international collaboration as well as promote public-private partnerships. Although the COVID-19 pandemic has significantly boosted genomics capacity in Africa, the continent still lags other regions. Here, we highlighted key initiatives in genomics research and efforts to address health challenges facing the diverse and fast-growing populations on the continent. We explore the scalability of genomic tools and techniques to tackle a broader range of infectious diseases in Africa, a continent that desperately requires a boost from genomic science., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)