Herbicide-resistant (HR) crops, specifically glyphosate-, glufosinate-, and dicamba-resistant (HT3) soybean, will offer producers a new weed management option for the control of some HR weeds in soybean. Four field experiments were conducted near Cottam and on Walpole Island, ON, Canada, during 2017 and 2018 to assess the control of multiple-resistant (MR) waterhemp (herbicide groups 2, 5, and 9) in HT3 soybean treated with various herbicide programs. Pyroxasulfone/flumioxazin, flumioxazin plus metribuzin, or S-metolachlor/metribuzin applied preemergence (PRE) and followed by (fb) glyphosate postemergence (POST) controlled MR waterhemp at 94%, 66%, and 78%, respectively, in early September. Pyroxasulfone/flumioxazin, flumioxazin plus metribuzin, or S-metolachlor/metribuzin applied PRE controlled MR waterhemp 86%–97% when fb glufosinate POST; 100% when fb glyphosate plus dicamba POST; 99%–100% when fb glufosinate plus dicamba POST; and 100% when fb glyphosate plus dicamba POST and fb glufosinate POST2 (before the R2 soybean growth stage) in early September. Reduced MR waterhemp interference with all herbicide programs resulted in an increase in HT3 soybean yield (up to 59%) relative to the weedy control. Results indicate that pyroxasulfone/flumioxazin, flumioxazin plus metribuzin, or S-metolachlor/metribuzin applied PRE fb glufosinate POST, glyphosate plus dicamba POST, glufosinate plus dicamba POST, or glyphosate plus dicamba POST fb glufosinate POST2 provides similar and excellent season-long control of MR waterhemp in HT3 soybean.