Field studies were conducted in 2016 and 2017 at Clinton, NC, to quantify the effects of season-long interference of large crabgrass [Digitaria sanguinalis (L.) Scop.] and Palmer amaranth (Amaranthus palmeri S. Watson) on ‘AG6536’ soybean [Glycine max (L.) Merr.]. Weed density treatments consisted of 0, 1, 2, 4, and 8 plants m−2 for A. palmeri and 0, 1, 2, 4, and 16 plants m−2 for D. sanguinalis with (interspecific interference) and without (intraspecific interference) soybean to determine the impacts on weed biomass, soybean biomass, and seed yield. Biomass per square meter increased with increasing weed density for both weed species with and without soybean present. Biomass per square meter of D. sanguinalis was 617% and 37% greater when grown without soybean than with soybean, for 1 and 16 plants m−2 respectively. Biomass per square meter of A. palmeri was 272% and 115% greater when grown without soybean than with soybean for 1 and 8 plants m−2, respectively. Biomass per plant for D. sanguinalis and A. palmeri grown without soybean was greatest at the 1 plant m−2 density. Biomass per plant of D. sanguinalis plants across measured densities was 33% to 83% greater when grown without soybean compared with biomass per plant when soybean was present for 1 and 16 plants m−2, respectively. Similarly, biomass per plant for A. palmeri was 56% to 74% greater when grown without soybean for 1 and 8 plants m−2, respectively. Biomass per plant of either weed species was not affected by weed density when grown with soybean due to interspecific competition with soybean. Yield loss for soybean grown with A. palmeri ranged from 14% to 37% for densities of 1 to 8 plants m−2, respectively, with a maximum yield loss estimate of 49%. Similarly, predicted loss for soybean grown with D. sanguinalis was 0 % to 37% for densities of 1 to 16 m−2 with a maximum yield loss estimate of 50%. Soybean biomass was not affected by weed species or density. Results from these studies indicate that A. palmeri is more competitive than D. sanguinalis at lower densities, but that similar yield loss can occur when densities greater than 4 plants m−2 of either weed are present.