Grain size, grain number per panicle, and grain weight are crucial determinants of yield-related traits in cereals. Understanding the genetic basis of grain yield-related traits has been the main research object and nodal in crop science. Sorghum and maize, as very close C4 crops with high photosynthetic rates, stress tolerance and large biomass characteristics, are extensively used to produce food, feed, and biofuels worldwide. In this review, we comprehensively summarize a large number of quantitative trait loci (QTLs) associated with grain yield in sorghum and maize. We placed great emphasis on discussing 22 fine-mapped QTLs and 30 functionally characterized genes, which greatly hinders our deep understanding at the molecular mechanism level. This review provides a general overview of the comprehensive findings on grain yield QTLs and discusses the emerging trend in molecular marker-assisted breeding with these QTLs.