Residual herbicides are routinely recommended to aid in control of glyphosate-resistant (GR) Palmer amaranth in cotton. Acetochlor, a chloroacetamide herbicide, applied PRE, controls Palmer amaranth. A microencapsulated (ME) formulation of acetochlor is now registered for PRE application in cotton. Field research was conducted in North Carolina to evaluate cotton tolerance and Palmer amaranth control by acetochlor ME alone and in various combinations. Treatments, applied PRE, consisted of acetochlor ME, pendimethalin, or no herbicide arranged factorially with diuron, fluometuron, fomesafen, diuron plus fomesafen, and no herbicide. The PRE herbicides were followed by glufosinate applied twice POST and diuron plus MSMA directed at layby. Acetochlor ME was less injurious to cotton than pendimethalin. Acetochlor ME alone or in combination with other herbicides reduced early season cotton growth 5 to 8%, whereas pendimethalin alone or in combinations injured cotton 11 to 13%. Early season injury was transitory, and by 65 to 84 d after PRE treatment, injury was no longer noticeable. Before the first POST application of glufosinate, acetochlor ME and pendimethalin controlled Palmer amaranth 84 and 64%, respectively. Control by acetochlor ME was similar to control by diuron plus fomesafen and greater than control by diuron, fluometuron, or fomesafen alone. Greater than 90% control was obtained with acetochlor ME mixed with diuron or fomesafen. Palmer amaranth control was similar with acetochlor ME plus a full or reduced rate of fomesafen. Acetochlor ME controlled large crabgrass and goosegrass at 91 and 100% compared with control at 83 and 91%, respectively, by pendimethalin. Following glufosinate, applied twice POST, and diuron plus MSMA, at layby, 96 to 99% control was obtained late in the season by all treatments, and no differences among herbicide treatments were noted for cotton yield. This research demonstrated that acetochlor ME can be safely and effectively used in cotton weed management programs.