Glycosyltransferases (GTs) are key enzymes that catalyze the transfer of sugar moieties to diverse acceptor molecules and play important roles in a wide range of biological processes, including plant growth, development, and environmental adaptation. However, glycosyltransferase family 4 (GT4), the second-largest GT family, remains poorly characterized in soybean. In this study, we identified 60 GT4 family members in the soybean genome based on sequence information from the CAZy database and systematically characterized their phylogenetic relationships, genomic organization, and expression patterns by integrating genomic and multidimensional transcriptomic data. Furthermore, using a previously established soybean ethyl methanesulfonate (EMS) mutant population, we identified GmSPS8 as a candidate gene potentially involved in the regulation of seed weight. Notably, natural variation and haplotype analyses revealed that GmSPS8 is located within a genomic region subject to domestication selection, suggesting its potential involvement in the evolutionary selection of soybean seed size. In sum, we systematically characterized the soybean GT4 gene family and identified GmSPS8 as a potential domestication-associated candidate gene for seed weight regulation, providing new insights into the functional characterization of soybean GT4 family members and the identification and utilization of genes associated with soybean yield-related traits.