Abstract The seed oil‐to‐protein ratio has increased remarkably during soybean domestication; however, the principal genetic determinants governing this critical agronomic trait remain elusive. Integrated genome‐wide and transcriptome‐wide association studies (GWAS/TWAS) are conducted and identified GmSop20 on chromosome 20 as a pivotal regulator of soybean seed oil and its protein content. Genetic diversity analysis reveals a domestication‐selected allele, GmSop20 C , which has undergone intense artificial selection and is dominant in cultivars across northern China and the USA. This allele drives a substantial increase in the oil‐to‐protein ratio from 0.35 in ancestral lines to 0.47 in cultivars. Functional validation reveals that the knockout of GmSop20 significantly reduces the ratio to 0.19, while its overexpression increases it to 0.64. Notably, while mutant lines exhibit a modest increase in total oil and protein content, overexpression maintains stable compositional levels. Mechanistically, GmSop20 directly activates GmSWEET10a expression, synergizing two artificially selected loci within a unified regulatory network to amplify sugar allocation from the seed coat to the embryo, thereby enhancing oil accumulation. The findings establish GmSop20 as a master regulator of seed composition and provide insights for custom‐designing soybean nutritional profiles, enabling the precise regulation of the oil‐to‐protein ratio through targeted manipulation of this key genetic module.