Managing weeds in watermelon is challenging because of the limited availability of herbicides approved for use in this crop. Field experiments on efficacy and crop tolerance were conducted to determine the potential for halosulfuron use in watermelon in Georgia and North Carolina. Halosulfuron was applied PRE, early POST (EPOST; one-leaf watermelon), and late POST (LPOST; watermelon with 30-cm runners) at 26, 39, and 52 g ai/ha. Under weed-free conditions, PRE treatments did not injure watermelon. EPOST and LPOST treatments caused 45 and 34% injury 2 wk after treatment, respectively, averaged over halosulfuron rate. EPOST treatments reduced watermelon fruit number and total weight by 15 and 22%, respectively, and LPOST treatments reduced total fruit weight 12%. Halosulfuron PRE at 39 or 52 g/ha provided 94% or greater control of carpetweed, Palmer amaranth, and smooth pigweed. EPOST treatments controlled 84 and 88% of yellow nutsedge and smooth pigweed, respectively, but LPOST treatments controlled less than 83% of all weed species. Sequential applications of halosulfuron at 26 g/ha PRE and 26 g/ha LPOST controlled 89 to 99% of carpetweed, coffee senna, Palmer amaranth, smooth pigweed, and yellow nutsedge. Our data suggest growers can effectively use halosulfuron PRE in seeded watermelon. However, POST applications should be made only after watermelon has 30-cm runners and as a salvage spot treatment where previous weed control strategies have failed to provide adequate control.