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Hybrid breeding can increase the competitiveness of wheat (Triticum aestivum L.) in Sub-Saharan Africa by fostering more public-private partnerships and promoting investment by the private sector. The benefit of hybrid wheat cultivars in South Africa has previously been demonstrated but due to the high cost of hybrid seed production, hybrid breeding has not received significant attention in the past decade. Considering the renewed commitment of the private sector to establish wheat as a hybrid crop globally, coupled with significant research investment into enhancement of outcrossing of wheat, hybrid wheat breeding in Southern and Eastern Africa should be revisited. Our study aimed to identify genetically distinct germplasm groups in spring wheat that would be useful in the establishment of heterotic pools targeting this region. Multi-environment yield testing of a large panel of F1 test hybrids, generated using global elite germplasm, was carried out between 2019 and 2020 in Argentina, Africa, Europe, and Australia. We observed significant genotype by environment interactions within our testing network, confirming the distinctiveness of African trial sites. Relatively high additive genetic variance was observed highlighting the contribution of parental genotypes to the grain yield of test hybrids. We explored the genetic architecture of these parents and the genetic factors underlying the value of parents appear to be associated with their genetic subgroup, with positive marker effects distributed throughout the genome. In testcrosses, elite germplasm from the International Maize and Wheat Improvement Center (CIMMYT) appear to be complementary to the genetically distinct germplasm bred in South Africa. The feasibility of achieving genetic gain via heterotic pool establishment and divergence, and by extension the viability of hybrid cultivars in Sub-Saharan Africa, is supported by the results of our study. [ABSTRACT FROM AUTHOR]