Residual herbicides applied throughout the season are critical for the control of weeds in Georgia peanut and cotton. Pyroxasulfone inhibits very long chain fatty acid synthesis in plants and is a highly effective residual herbicide for control of annual grasses and broadleaf weeds and would be an effective resistance management tool to rotate with PPO herbicides. Trials were conducted in Georgia to evaluate peanut and cotton tolerance to pyroxasulfone. Pyroxasulfone applied preemeregence (PRE) or postemergence (POST) to three-leaf cotton caused undesirable injury, and yield loss. Pyroxasulfone applied PRE to peanut caused significant early season stunting in one of two trials; differences likely in response to rainfall quantities at planting. Peanut recovered by pod set and yield was not reduced by a 1X rate of pyroxasulfone (120 g ai/ha). However, yield was reduced 7% following a 2X rate. Peanut tolerance is excellent to pyroxasulfone applied POST to peanut from emergence through pod set. Due to the potential for undesirable injury and yield loss, pyroxasulfone applied to cotton PRE or POST or peanut PRE is not recommended. Intercropping cucurbits and cotton has the potential to improve grower profits over traditional monoculture practices since crops share resources and production costs. However, developing effective programs to control weeds with herbicides that are tolerant to both crops can be challenging. Three trials were conducted to (1) identify herbicide systems to manage Palmer amaranth when intercropping cucurbits with cotton and to (2) determine the profitability of intercropping cantaloupe or watermelon with cotton. Fomesafen applied prior to melon transplant controlled Palmer amaranth (>85%). Watermelon exhibits excellent tolerance to fomesafen while transient early season injury was observed in cantaloupe. Intercropping systems that controlled Palmer amaranth at least 85% produced cantaloupe or watermelon yields equal to the weed-free monoculture system but produced seed cotton yields that were 11 to 18% less when compared to weed-free monoculture cotton. Although cotton production was less in the intercropping system when compared to the monoculture system, revenue from intercropping systems exceeded those of cantaloupe or watermelon monoculture 17 to 18%, as long as Palmer amaranth was controlled.