Field studies were conducted at three locations to evaluate glyphosate-resistant (GR) cotton response, weed control, and cotton lint yields to two formulations of glyphosate (diammonium salt– glyphosate and isopropylamine salt–glyphosate) and trifloxysulfuron applied early postemergence (EPOST) alone or to tank mixtures of trifloxysulfuron with each glyphosate formulation, with and without a late postemergence-directed (LAYBY) treatment of prometryn plus MSMA. Trifloxysulfuron and both formulations of glyphosate controlled common lambsquarters and pitted morningglory. Both glyphosate formulations provided equivalent control of common lambsquarters, goosegrass, pitted morningglory, prickly sida, and smooth pigweed. Trifloxysulfuron controlled smooth pigweed better than either glyphosate formulation but did not control goosegrass or prickly sida. Prometryn plus MSMA LAYBY improved late-season control of common lambsquarters, goosegrass, large crabgrass, and pitted morningglory for all EPOST systems and improved late-season smooth pigweed control for EPOST systems that did not include trifloxysulfuron. Cotton injury was 2% or less from both glyphosate formulations, while trifloxysulfuron injured ‘Deltapine 5415RR’ 7 to 16% at two locations. At a third location, trifloxysulfuron injured ‘Paymaster 1218RR/BG’ 24%, and when applied in mixture with either glyphosate formulation, injury increased to at least 72%. Cotton injury was transient at the first two locations and was not visually apparent 3 to 5 wk later. Cotton yield at the third location was reduced. High cotton yields reflected high levels of weed control.