Seed weight is a key component of crop yield. However, molecular mechanisms underlying soybean seed weight variation remain largely elusive. Here, we identify a major seed weight determining gene Glycine max SMALL SEED 6 (GmSMS6) that encodes a 14-3-3 protein. GmSMS6 physically and genetically interacts with the transcription factor GmbZIP151 and the RING-type E3 ligase GmUBQ1. GmSMS6 acts as a regulatory hub switch that coordinates the transcriptional activation activity and GmUBQ1-mediated stability of GmbZIP151, primarily repressing cellular expansion of soybean cotyledons. Knocking out GmSMS6 increases seed weight and protein content but decreases oil accumulation in multiple soybean genetic backgrounds. A loss-of-function allele of GmSMS6 is absent in available soybean resources, while the weakly expressed haplotype associated with heavy seed weight has undergone selection in G. max. These results provide insights into mechanisms underlying soybean domestication and highlight the importance of gene loss for improving crop yield and quality.