Abstract: Although traditional selective breeding has had a tremendous impact on both livestock and crop production in Africa, this has not kept pace with the high demand for animal and plant products on account of increasing urbanization, improved livelihoods and a rapidly growing human population. These challenges justify the need for more innovative and sustainable ways of improving animal and crop production to meet this demand. Over the last two decades the potential of genomics as a key tool to achieve improvement in desirable phenotypic traits has revolutionized the field of applied animal and plant biology. However, well informed use of such techniques has yet to be fully exploited within the context of local resources and capacity-building. The objective of this review is to highlight the rich agricultural biodiversity of sub-Saharan Africa, the potential of genomics in their sustainable use for food security, the challenges of genomic research and the strategies that can be adopted to overcome them in the implementation of agricultural genomic research in Africa. The lack of state-of-the-art laboratory research facilities, skilled human resources, poor funding and non-availability of scientific research resources, paucity of collaborative links between African researchers and a lack of engagement between key stakeholders in the agricultural value chain were identified as major barriers that affect agricultural genomic research in Africa. Finally, the recommended strategies to overcome these challenges will guide policy-makers, researchers, development partners and key stakeholders in the smooth advancement of sustainable agricultural genomic research for improved food security in Africa.