Greater soybean (Glycine max L. Merr.) total dry matter (TDM) production may support yield potential and correspondingly drive greater nutrient uptake. Whether increased dry matter (DM) and reduced interplant competition at decreased seeding rates improves grain yield response to fertilizer applications is not clear. A 3-site-year trial was conducted to evaluate soybean seeding rates and fertilizer applications on plant growth, nutrient accumulation, grain yield, and economic return. Seeding rates included: 123,500; 222,400; 321,200; and 420,100 seeds ha −1 . Fertilizer applications consisted of: unfertilized; 90 kg MOP (0−0−62 N−P−K) ha −1 pre-plant incorporated (PPI); 168 kg MESZ (12-40−0−10−1 N−P−K−S−Zn) ha −1 applied 5 by 5 cm below and to the side of the seed at planting (5 × 5); and 90 kg MOP ha −1 PPI and 168 kg MESZ ha −1 applied 5 × 5. Dry matter (V4) increased 37.7 to 116.6% and 73.3 to 137.5% with seeding rates ≥222,400 seeds ha −1 and MESZ applications, respectively, with greater early-season DM supporting increased nutrient uptake and grain yield potential. Increasing seeding rate from 123,500 to 222,400 seeds ha −1 improved grain yield 9% but no differences were observed above 222,400 seeds ha −1 .The MESZ and MOP+MESZ applications increased grain yield 7.4 and 6.9%, respectively, while MOP did not affect grain yield across site-years. As emphasis on creating more durable, resilient agroecosystems continues, results suggest seeding rates ≥222,400 seeds ha −1 maximized DM accumulation facilitating nutrient uptake which may be paramount to improving fertilizer management or reducing post-harvest residual soil nutrients in impaired watersheds or regions of greater nutrient loss potential. Abbreviations: 5 × 5, subsurface band placement 5-cm below and laterally; BNF, biological nitrogen fixation; DM, dry matter; HI, harvest index; MESZ, 12−40−0−10−1 N−P−K−S−Zn; MOP, 0−0−62 N−P−K; PPI, pre-plant incorporated; R5DM, R5 dry matter; R8TDM, R8 total dry matter; SOM, soil organic matter; TDM, total dry matter; V4DM, V4 dry matter.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.