Studies were conducted to determine the tolerance of sweetpotato and Palmer amaranth control to a premix of flumioxazin and pyroxasulfone pretransplant (PREtr) followed by (fb) irrigation. Greenhouse studies were conducted in a factorial arrangement of four herbicide rates (flumioxazin/pyroxasulfone PREtr at 105/133 and 57/72 g ai ha–1, S-metolachlor PREtr 803 g ai ha–1, nontreated) by three irrigation timings [2, 5, and 14 d after transplanting (DAP)]. Field studies were conducted in a factorial arrangement of seven herbicide treatments (flumioxazin/pyroxasulfone PREtr at 40/51, 57/72, 63/80, and 105/133 g ha–1, 107 g ha–1 flumioxazin PREtr fb 803 g ha–1S-metolachlor 7 to 10 DAP, and season-long weedy and weed-free checks) by three 1.9-cm irrigation timings (0 to 2, 3 to 5, or 14 DAP). In greenhouse studies, flumioxazin/pyroxasulfone reduced sweetpotato vine length and shoot and storage root fresh biomass compared to the nontreated check and S-metolachlor. Irrigation timing had no influence on vine length and root fresh biomass. In field studies, Palmer amaranth control was≥91% season-long regardless of flumioxazin/pyroxasulfone rate or irrigation timing. At 38 DAP, sweetpotato injury was≤37 and≤9% at locations 1 and 2, respectively. Visual estimates of sweetpotato injury from flumioxazin/pyroxasulfone were greater when irrigation timing was delayed 3 to 5 or 14 DAP (22 and 20%, respectively) compared to 0 to 2 DAP (7%) at location 1 but similar at location 2. Irrigation timing did not influence no.1, jumbo, or marketable yields or root length-to-width ratio. With the exception of 105/133 g ha–1, all rates of flumioxazin/pyroxasulfone resulted in marketable sweetpotato yield and root length-to-width ratio similar to flumioxazin fb S-metolachlor or the weed-free checks. In conclusion, flumioxazin/pyroxasulfone PREtr at 40/51, 57/72, and 63/80 g ha–1 has potential for use in sweetpotato for Palmer amaranth control without causing significant crop injury and yield reduction.