Field studies were conducted at two locations in North Carolina in 1999 and 2000 to evaluate weed and bromoxynil-resistant cotton response to bromoxynil, pyrithiobac, and MSMA applied early postemergence (EPOST), alone or mixtures in all combinations (two way and three way), and to prometryn plus MSMA applied late postemergence directed (LAYBY). Trifluralin preplant incorporated followed by fluometuron preemergence controlled common lambsquarters, eclipta, and smooth pigweed at least 90%. These herbicides also provided greater than 90% common ragweed control at two locations but only 65% control at a third location. Pyrithiobac and pyrithiobac plus MSMA EPOST increased sicklepod control more than did bromoxynil or bromoxynil plus MSMA EPOST. Bromoxynil and pyrithiobac were more effective for sicklepod control when applied in mixture with MSMA. Bromoxynil plus pyrithiobac EPOST or with MSMA controlled (≥ 90%) common lambsquarters, common ragweed, entireleaf morningglory, prickly sida, and smooth pigweed early season. But the LAYBY treatment of prometryn plus MSMA frequently improved late-season control of entireleaf morningglory, large crabgrass, prickly sida, and sicklepod. A tank mixture of MSMA plus bromoxynil or pyrithiobac and the three-component tank mixture (bromoyxnil, MSMA, plus pyrithiobac) provided a broader weed control spectrum than did either bromoxynil or pyrithiobac alone. Cotton lint yields were increased with all postemergence systems, and the LAYBY treatment of prometryn plus MSMA increased cotton yields in 13 out of 16 comparisons. High cotton yields were indicative of high levels of weed control.