Chemical options for weed control in commercial cowpea production are limited. Repeated long-term use of the acetolactate synthase (ALS) inhibitor, imazethapyr, has resulted in selection for ALS-resistant populations of Palmer amaranth. Experiments were conducted at Bixby, OK, and Kibler, AR, from 2001 to 2003 to evaluate the tolerance of cowpea cultivars and advanced breeding lines to fomesafen, a potential alternative for controlling ALS-resistant Palmer amaranth and other problematic broadleaf weeds. Eight commercial cultivars and 42 advanced breeding lines were entered in the preliminary screening, using 0.84 kg/ha fomesafen. Six breeding lines were selected for the first replicated trial and three (00-582, 00-584, and 00-609) were advanced to across-location experiments. Fomesafen doses of 0, 0.17, 0.34, and 0.67 kg/ha were tested across locations. ‘Early Scarlet’ was used as commercial standard. The advanced lines had equal or higher yield potential (1,182 to 1,936 kg/ha) than Early Scarlet (1,108 kg/ha) across locations. Of the cultivars tested, line 00-609 was the best yielder, whereas 00-584 had the highest tolerance to fomesafen. At the commercial fomesafen rate of 0.34 kg/ha, 00-584 had higher yield (974 and 1,735 kg/ha, respectively, at Bixby, OK, and Kibler, AR) than the nontreated, weed-free, Early Scarlet. Thus, fomesafen can be used on the tolerant line, 00-584, without reducing yield potential relative to Early Scarlet.