Five studies were conducted at Clayton, Rocky Mount, and Lewiston-Woodville, NC, in 2001 and 2002, to evaluate weed management, crop tolerance, and yield in strip- and conventional-tillage glyphosate-resistant cotton. Cotton was treated with two glyphosate formulations; glyphosate-IP (isopropylamine salt) or glyphosate-TM (trimethylsulfonium salt), early postemergence (EPOST) alone or in a mixture with S-metolachlor. Early season cotton injury was minimal (3%) with either glyphosate formulation alone or in mixture with S-metolachlor. Weed control and cotton yields were similar for both glyphosate formulations. The addition of S-metolachlor to either glyphosate formulation increased control of broadleaf signalgrass, goosegrass, large crabgrass, and yellow foxtail 14 to 43 percentage points compared with control by glyphosate alone. S-metolachlor was not beneficial for late-season control of entireleaf morningglory, jimsonweed, pitted morningglory, or yellow nutsedge. The addition of S-metolachlor to either glyphosate formulation increased control of common lambsquarters, common ragweed, Palmer amaranth, smooth pigweed, and velvetleaf 6 to 46 percentage points. The addition of a late postemergence-directed (LAYBY) treatment of prometryn plus MSMA increased control to greater than 95% for all weed species regardless of EPOST treatment, and control was similar with or without S-metolachlor EPOST. Cotton lint yield was increased 220 kg/ha with the addition of S-metolachlor to either glyphosate formulation compared with yield from glyphosate alone. The addition of the LAYBY treatment increased yields 250 and 380 kg/ha for glyphosate plus S-metolachlor and glyphosate systems, respectively. S-metolachlor residual activity allowed for an extended window for more effective LAYBY application to smaller weed seedlings instead of weeds that were possibly larger and harder to control.