There is little information on the efficacy and profitability of two-pass weed control strategies in soybean when a preemergence (PRE) residual herbicide is followed by glyphosate applied late postemergence (LPOST) under Ontario, Canada environmental conditions. Ten field trials were conducted during 2011-2013 in Ontario, Canada to determine the level of weed control, yield and net returns of various preemergence/postemergence programs in glyphosate-resistant soybean. Crop injury was 2% or less with the herbicides evaluated except for chlorimuron + flumioxazin (PRE) and pyroxasulfone + flumioxazin (PRE) which caused 4% and 7% visible injury in soybean, respectively. A single application of glyphosate resulted in variable weed control (73% - 98%) while the sequential application of glyphosate provided excellent weed control (98% - 100%). The control of all weeds 8 WAA after the LPOST glyphosate application was equivalent regardless of the PRE herbicide applied (96% - 100%). Soybean yield was equivalent to the weed free control regardless of the PRE herbicide applied. Soybean yield was lower than the sequential application of glyphosate with chlorimuron or pyroxasulfone/flumioxazin PRE fb glyphosate LPOST. Generally net return with the two-pass programs was equivalent to the sequential application of glyphosate. Net returns were lower than the sequential application of glyphosate with chlorimuron or s-metolachlor + flumetsulam followed by glyphosate LPOST. Based on these results, a sequential application of glyphosate or a two-pass program of a preemergence residual herbicide followed by glyphosate LPOST are the preferred weed management programs in glyphosate-resistant soybean. The two-pass programs have the potential to reduce selection pressure for glyphosate-resistant weeds.