Weed management is an important component of sweetpotato production. Currently, S-metolachlor is the only herbicide registered in sweetpotato that has some suppressive effect on nutsedge species (Cyperus spp.). It is integral that the release of any new germplasm from sweetpotato breeding programs be tolerant to S-metolachlor. Screening for thousands of experimental clones for S-metolachlor in a field trial would be cumbersome. Therefore, screening for tolerant lines might be streamlined in an hydroponics system. Research was conducted to determine whether a hydroponics assay could detect differences in S-metolachlor response between a known sensitive sweetpotato cultivar (Centennial) and a tolerant sweetpotato cultivar (Beauregard) in 10 days. Results of the study show that ‘Beauregard’ was ≈50 times more tolerant to S-metolachlor than ‘Centennial’ when accessing injury at the 25% threshold. No differences were detected in S-metolachlor response between cultivars in the soil-based assay. This assay could be used for screening for S-metolachlor tolerance in a sweetpotato breeding program.