Pre-harvest sprouting of wheat is the premature germination of ripened wheat (Triticum aestivum L.) kernels in the spike before harvest and is influenced by a combination of environmental and genetic factors, and their interaction. This greatly affects grain yield and quality, thus posing a threat to food security and sustainable agriculture. Pre-harvest sprouting has been studied for over 30 years in South Africa and remains a trait of interest in our wheat breeding programs amid climatic change. This paper therefore provides a comprehensive review of the progress made, as well as the challenges and limitations encountered, in breeding wheat for pre-harvest sprouting tolerance in South Africa. Future prospects and research directions are also discussed. Conventional breeding has been the main breeding strategy used in the country, with the success of breeding commercial wheat cultivars with durable pre-harvest sprouting tolerance for deployment in the three main wheat production regions of South Africa. Therefore, augmenting conventional breeding with molecular markers and modern genomic breeding technologies is anticipated to speed up breeding locally adapted, climate-resilient wheat varieties that balance tolerance to pre-harvest sprouting with high yield potential. This is key to realizing sustainable development goals of food security and sustainable agriculture.