Glyphosate-resistant Palmer amaranth (Amaranthus palmeri S Wats.) has increased the need for effective preemergence (PRE) herbicides in cotton (Gossypium hirsutum L.). Fluridone, a carotenoid biosynthesis inhibitor, has a mechanism of action currently not used in crops. Field research focused on Palmer amaranth control by fluridone (224 g a.i. ha-1) applied PRE alone and in combination with acetochlor, diuron, pendimethalin, and half and full rates of fomesafen (1260, 560, 1063, 140, and 280 g a.i. ha-1, respectively). Also evaluated were fluridone (112 and 168 g ha-1) plus fomesafen 140 g ha-1, diuron 560 g ha-1 plus fomesafen 140 or 280 g ha-1, and acetochlor 1260 g ha-1 plus fomesafen 140 or 280 g ha-1. PRE herbicides were followed by glufosinate applied twice postemergence (POST) and diuron plus MSMA at layby. Fluridone injured cotton 3% or less and did not increase injury when combined with other herbicides. Palmer amaranth was controlled 97% by fluridone at 224 g ha-1 prior to glufosinate application compared with 87 to 95% control by acetochlor, diuron, fomesafen, or pendimethalin. Fluridone alone controlled Palmer amaranth as well as acetochlor plus fomesafen and better than diuron plus fomesafen. Similar control was obtained with fluridone at 112, 168, and 224 g ha-1, acetochlor, or diuron plus fomesafen at 140 g ha-1. Glufosinate controlled emerged weeds but continued emergence was noted in the absence of residual herbicides. PRE herbicides increased control prior to layby but did not increase cotton yield. This research demonstrated that fluridone can be used in a glufosinate-based system for proactive resistance management.