Increasing soybean production and ensuring greater access to soybean protein and lipids is critical for global food security and human health. Seed size (i.e., seed weight) is one of the most important agronomic traits of soybean, which not only determines the seed yield, but can also affect the yield of protein and lipids. In China, farmers favor soybean cultivars with large seeds, which they believe produce more protein and lipids; however, experimental evidence supporting this belief is lacking. Therefore, we conducted field experiments from 2017 to 2020 at 35 locations across the Huang-Huai-Hai region (HHH) of China with 64 soybean cultivars. The seed yield, seed protein content, and seed lipids content of soybean, and their relationship with seed size were investigated. The highest seed yield (i.e., seed weight per unit area) was 2996.5 kg ha−1 in the north of HHH. However, the highest seed protein content was found in the south of HHH (42.5%) for the higher temperature, which was significantly higher than that of the middle (41.7%) and north of HHH (40.2%). In contrast, the highest seed lipids content was 20.7% in the north of HHH. Temperature, which had a path coefficient on seed yield of 0.519, can promote soybean seed yield. The correlation analysis indicated that the selection of the large seed size cultivar did not increase seed yield, and even led to a reduction of seed yield under high-yield environmental conditions. The seed protein content of soybean was not increased in the cultivars with large seed sizes. In addition, under different levels of seed lipids content (<20.30% or >20.30%), a significantly negative relationship was found between seed lipids content and hundred seed weight. Therefore, it is recommended that farmers choose to plant cultivars with smaller soybean seed sizes, so as to ensure high and stable soybean seed yield and obtain more vegetable protein and lipids per unit area.