A greenhouse experiment was conducted to evaluate the herbicidal activity of five aliphatic (ethyl, propyl, butyl, allyl, and 3-methylthiopropyl) and three aromatic (phenyl, benzyl, 2-phenylethyl) isothiocyanates on Texas panicum, large crabgrass, and sicklepod. All isothiocyanates were applied to soil at 0, 10, 100, 1,000, and 10,000 nmol g−1 of soil and incorporated. Weed emergence was generally stimulated at the lower isothiocyanate concentrations, but all isothiocyanates provided 37% or more suppression of each species at the highest concentration. Propyl and allyl isothiocyanate were most effective in suppressing Texas panicum, with 50% effective dose (ED50) values of 345 and 409 nmol g−1 of soil. All aliphatic isothiocyanates reduced Texas panicum density by at least 98%. Allyl and 3-methylthiopropyl isothiocyanate were the most effective aliphatics on large crabgrass, with density reductions of 98 and 100%, respectively. All aromatic isothiocyanates reduced large crabgrass density by 86 to 96%. Sicklepod was generally the most tolerant of the three species evaluated, with ED50 values for ethyl, propyl, and butyl isothiocyanate being greater than the evaluated concentrations. Maximum reduction in sicklepod density was 72, 68, 65, and 62%, which was achieved with allyl, benzyl, 3-methylthiopropyl, and phenyl isothiocyanate, respectively. This research shows that soil-applied and incorporated isothiocyanates are effective in suppressing some important weeds of the southeastern United States, but effectiveness of each isothiocyanate varies among species. Application techniques that minimize loss of volatile isothiocyanates may further improve their potential as an effective means of controlling these and other troublesome weeds.