Understanding the molecular mechanisms that regulate grain yield is important for improving agricultural productivity. Protein ubiquitination controls various aspects of plant growth but lacks understanding on how E2-E3 enzyme pairs impact grain yield in major crops. Here, we identified a RING-type E3 ligase SGD1 and its E2 partner SiUBC32 responsible for grain yield control inSetaria italica. The conserved role ofSGD1was observed in wheat, maize, and rice. Furthermore, SGD1 ubiquitinates the brassinosteroid receptor BRI1, stabilizing it and promoting plant growth. Overexpression of an eliteSGD1haplotype improved grain yield by about 12.8% per plant, and promote complex biological processes such as protein processing in endoplasmic reticulum, stress responses, photosystem stabilization, and nitrogen metabolism. Our research not only identifies the SiUBC32-SGD1-BRI1 genetic module that contributes to grain yield improvement but also provides a strategy for exploring key genes controlling important traits in Poaceae crops using the Setaria model system.