Purple nutsedge (Cyperus rotundus) is a troublesome weed in vegetable crops in the southern United States. Methyl bromide is widely used for effective purple nutsedge control in polyethylene-mulched vegetable crops. With the impending ban on methyl bromide in the United States, an effective alternative is needed. Laboratory and greenhouse experiments were conducted to determine the effect of phenyl isothiocyanate (ITC) concentration and exposure period on purple nutsedge tuber viability and to compare the retention of phenyl ITC in soil under low-density polyethylene (LDPE) and virtually impermeable film (VIF) mulches. Additionally, field experiments were conducted to evaluate the effectiveness of phenyl ITC under VIF mulch against purple nutsedge. A phenyl ITC concentration of 676 ppm in soil for 3 days in a sealed environment reduced purple nutsedge tuber viability by 97% compared with a nontreated control. Phenyl ITC retention was higher in soil covered with VIF mulch than with LDPE mulch. The predicted half-life of phenyl ITC under LDPE and VIF mulch was 6.1 and 8.9 days, respectively. In field experiments, phenyl ITC at 1500 kg·ha−1 under VIF mulch suppressed purple nutsedge shoots and reduced viable tuber density ≥72%, but control was not as effective as methyl bromide at 390 kg·ha−1 (67% methyl bromide:33% chloropicrin). Therefore, phenyl ITC up to 1500 kg·ha−1 under a VIF mulch is not a viable alternative to methyl bromide for effective purple nutsedge control.