Field studies were conducted under full-season conventional tillage in Delaware and New Jersey to determine the critical time to apply glyphosate with or without residual herbicides for optimum weed control in glyphosate-resistant soybean (GRS). The residual herbicides tank-mixed with glyphosate (0.84 kg/ha) were clomazone (0.55 kg/ha) and imazethapyr (0.063 kg/ha). Herbicide application was made at cracking, unifoliate, and one- to six-trifoliate stages of GRS. Weeds varied in growth stages from preemergence (PRE) at cracking to an average height of 30 cm at the six-trifoliate stage of GRS. Herbicide activity varied by year and weed species. Herbicidal action was better under high (>125 mm/mo) than low (<100 mm/mo) rainfall regime. Glyphosate application without residual herbicides was less effective at cracking and unifoliate than at one- to three-trifoliate leaf stages. Mixing residual herbicides with glyphosate at cracking and unifoliate stages enhanced weed control but made no difference when application was delayed until one- to three-trifoliate stages. For optimum weed control in GRS, the window of application for glyphosate alone was between the one- and three-trifoliate leaf stages, approximately 18 to 28 days after planting (DAP). If glyphosate was tank-mixed with residual herbicides, the window of application extended from cracking until the four-trifoliate stage; and weed interference until the four-trifoliate stage (approximately 32 DAP) did not depress GRS yield.