Field studies were conducted to determine watermelon tolerance and yield response when treated with bicyclopyrone preplant (PREPLANT), POST, and POST-directed (POST-DIR). Treatments consisted of two rates of bicyclopyrone (37.5 and 50 g ai ha–1), fomesafen (175 g ai ha–1), S-metolachlor (802 g ai ha–1), and a nontreated check. Preplant treatments were applied to formed beds 1 d prior to transplanting and included bicyclopyrone (37.5 and 50 g ha–1) and fomesafen (175 g ha–1), and new polyethylene mulch was subsequently laid above treated beds. POST and POST-DIR treatments were applied 14 ± 1 d after watermelon transplanting and included bicyclopyrone (37.5 and 50 g ha–1) POST and POST-DIR, and S-metolachlor (802 g ai ha–1) POST-DIR. POST-DIR treatments were applied to row middles, ensuring that no herbicide contacted watermelon vines or polyethylene mulch. At 2 wk after transplanting (WAT), 15% foliar bleaching was observed in watermelon treated with bicyclopyrone (50 g ha–1) PRE. At 3 WAT, bicyclopyrone (37.5 and 50 g ha–1) POST caused 16% and 17% foliar bleaching and 8% and 9% crop stunting, respectively. At 4 WAT, initial injury had subsided and bicyclopyrone (37.5 and 50 g ha–1) POST caused 4% and 4% foliar bleaching and 4% and 8% crop stunting, respectively. No symptoms of bleaching or stunting were observed at 6- and 8-WAT ratings. Watermelon total yield, marketable yield, total fruit number, marketable fruit number, and average fruit size were unaffected by herbicide treatments. Therefore, registration of bicyclopyrone (37.5 and 50 g ha–1) PREPLANT, POST, and POST-DIR would offer watermelon producers a safe herbicide option and a novel mode of action for weed management.