Greenhouse and field studies were conducted to evaluate potential interactions between glyphosate and trifloxysulfuron on barnyardgrass, browntop millet, hemp sesbania, seedling johnsongrass, pitted morningglory, prickly sida, sicklepod, and velvetleaf control as well as cotton injury and yield. In the greenhouse, glyphosate at 840 g ae/ha controlled all weed species 62 to 99%, which was better than trifloxysulfuron at 2.5 or 5 g ai/ha. Control of four-leaf pitted morningglory and hemp sesbania was 80 to 88% when glyphosate and trifloxysulfuron were mixed compared with 62 to 66% control with glyphosate alone. Mixing trifloxysulfuron with glyphosate did not affect control of other species compared with glyphosate alone. In the field, glyphosate controlled barnyardgrass, prickly sida, sicklepod, seedling johnsongrass, and velvetleaf 68 to 100%. Trifloxysulfuron controlled hemp sesbania, seedling johnsongrass, and sicklepod 65 to 88%. All other species were controlled 36 to 72% with glyphosate and 10 to 60% with trifloxysulfuron. Combinations of glyphosate (840 g/ha) and trifloxysulfuron (5 g/ha) were applied postemergence over-the-top and postemergence-directed to three-, six-, and nine-leaf glyphosate-resistant cotton in the field. Cotton injury at 2 wk after treatment (WAT) was less than 13% for all herbicide treatments and less than 5% by 3 WAT. Herbicides did not affect the percent of open bolls or nodes per plant. Seed cotton yield ranged from 1,430 to 1,660 kg/ha, and only the sequential over-the-top applications of trifloxysulfuron reduced cotton yield compared with the weed-free, nontreated cotton.