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Sesame production and productivity are severely constrained by a lack of high-yielding and locally adapted varieties, susceptibility to capsule shattering and low seed retention, biotic and abiotic stresses, and a lack of modern production and pre- and post-harvest technologies. Unimproved landraces are widely cultivated in sub-Saharan Africa, including Ethiopia. The landrace varieties are low yielders (<0.6 tons·ha−1), but they possess intrinsic seed oil quality characteristics, such as unique aroma and taste. Therefore, current and future sesame genetic improvement programs should integrate yield- and quality-promoting traits, local adaptation, amenability to machine harvesting, and other industrially essential food and feed attributes for multiple utilities. This can be achieved by integrating the conventional breeding methods, as well as genetic and genomic techniques such as mutation breeding and genomics-assisted breeding. Therefore, the objective of this review is to document the breeding progress, opportunities, and challenges of sesame with regard to genetic improvement, variety release, and deployment with enhanced seed yield and related agronomic traits, as well as oil content and fatty acid compositions. The review highlights sesame's economic values, production status, major production constraints, conventional breeding methods, and genomics-assisted breeding, as well as their integration, for accelerated breeding and cultivar development with market-preferred traits. [ABSTRACT FROM AUTHOR]