Palmer amaranth is an extremely troublesome weed for soybean growers because of its aggressive growth, adaptability, prolific seed production, and widespread resistance to many herbicides. Studies were initiated to determine the effects of herbicide application at first female inflorescence on Palmer amaranth control, biomass, seed production, cumulative germination, and seed viability. Enlist (2,4-D–resistant) soybean and Xtend (dicamba-resistant) soybean were planted and various combinations of either 2,4-D or dicamba with and without glufosinate and/or glyphosate were applied at first visible female Palmer amaranth inflorescence. Mixtures of 2,4-D + glufosinate and 2,4-D + glufosinate + glyphosate provided the greatest control at 4 wk after treatment in Enlist soybean. Similarly, in Xtend soybean, combinations of dicamba + glufosinate and dicamba + glufosinate + glyphosate provided the greatest control. The greatest reductions in biomass were from combinations of auxin herbicides (2,4-D or dicamba) plus glufosinate with and without glyphosate. Seed production was reduced most by treatments containing at least one effective site of action: an auxin herbicide (2,4-D or dicamba) or glufosinate. In contrast to previous research, cumulative germination and seed viability were not affected by herbicide treatments. This research indicates the efficacy of auxin herbicides or glufosinate alone and in combination to reduce the seed production of Palmer amaranth when applied at first female inflorescence. More research is needed to evaluate the full potential for applications of these herbicides at flower initiation to mitigate the evolution of herbicide resistance.