Palmer amaranth (Amaranthus palmeri) and common ragweed (Ambrosia artemisiifolia) are two of the most troublesome weeds in soybean. Both weeds possess widespread resistance to glyphosate and acetolactate synthase (ALS) inhibiting herbicides resulting in the use of protoporphyrinogen oxidase- (PPO) inhibitors to control these biotypes, although PPO-resistant biotypes are increasing. New soybean herbicide-resistant trait technologies enable novel herbicide combinations. Combinations of two herbicide sites-of-action (SOA) improved control 19 to 25% and 14 to 19% of Palmer amaranth and common ragweed, respectively, versus using one SOA (mesotrione, dicamba, 2,4-D, or glufosinate alone). Seed production of 5 to 10 cm Palmer amaranth and common ragweed was reduced greater than 76% by fomesafen, auxin (dicamba and 2,4-D), or glufosinate containing treatments. Some weeds survived and set seed even when treated at the proper size. As weed size increased from 10 to 30 cm, control diminished and fecundity increased, underscoring the importance of proper herbicide application timing. Effective preemergence herbicides reduced the number of weeds present at the postemergence application compared to no treatment, reducing the likelihood of herbicide resistance development. Dicamba, 2,4-D, or glufosinate applied alone or auxin + glufosinate combinations reduced Palmer amaranth seed production greater than 95% when applied at first visible female inflorescence; this first report, in addition to previous reports on individual herbicides, indicates this application timing may be useful for soil seed bank management. This research informs mitigation of herbicide resistance spread and development.