Waterhemp has evolved resistance to Group 2, 5, 9, 14, and 27 herbicides in Ontario, Canada, making control of this challenging weed even more difficult. Acetochlor is a Group 15, chloroacetanilide herbicide that has activity on many small-seeded annual grasses and some small-seeded annual broadleaf weeds, including waterhemp. The objective of this study was to ascertain if acetochlor mixtures with broadleaf herbicides (dicamba, metribuzin, diflufenican, sulfentrazone, or flumioxazin), applied preemergence (PRE), increase multiple-herbicide-resistant (MHR) waterhemp control in soybean. Five trials were conducted over 2 yr (2021 to 2022). The acetochlor mixtures caused ≤7% soybean injury, except acetochlor + flumioxazin, which caused 19% soybean injury. Acetochlor applied PRE controlled MHR waterhemp 89% at 4 wk after application (WAA). Dicamba, metribuzin, diflufenican, sulfentrazone, or flumioxazin controlled MHR waterhemp 59%, 67%, 58%, 64%, and 86%, respectively, at 4 WAA. Acetochlor applied in a mixture with dicamba, metribuzin, diflufenican, sulfentrazone, or flumioxazin provided good to excellent control of MHR waterhemp; control ranged from 91% to 98% but was similar to acetochlor applied alone. Acetochlor alone reduced MHR waterhemp density and biomass 98% and 93%; acetochlor + flumioxazin reduced waterhemp density and biomass by an additional 2% and 7%, respectively. This research concludes that acetochlor applied in a mixture with flumioxazin was the most efficacious mixture evaluated for MHR waterhemp control.