Separate field experiments were conducted to evaluate weed control and cotton response to flumioxazin in North Carolina. Flumioxazin postemergence directed (PD) at 70 g ai/ha applied alone or mixed with glyphosate or MSMA completely controlled common lambsquarters, common ragweed, entireleaf morningglory, ivyleaf morningglory, Palmer amaranth, pitted morningglory, prickly sida, sicklepod, smooth pigweed, and tall morningglory 4 wk after treatment. Glyphosate at 1,120 g ai/ha controlled sicklepod and entireleaf, ivyleaf, pitted, and tall morningglory less than flumioxazin. Weed-free experiments were conducted to evaluate cotton injury, fresh biomass reduction, and yield response to flumioxazin at 70 g ai/ha preplant (PP) and two rates PD. Nine PP applications were made at various timings between 0 and 10 wk prior to planting. Cotton was stunted 12% initially, and midseason cotton biomass was reduced when flumioxazin was applied at planting in 1 yr. Flumioxazin did not injure 15- or 30-cm–tall cotton when applied PD at 36 or 70 g/ha. Cotton yield differed between years, but was not affected by various flumioxazin treatments compared with commercial standards and nontreated controls.