Applying glyphosate relative to the growth stage of soybean is important for maximizing weed control and profits in glyphosate-resistant soybean under no-till systems. A study was conducted in Ontario for 4 yr to evaluate the effectiveness and gross return on the timing and sequence of applications of glyphosate in glyphosate-resistant no-till soybean. Percent control of various weed species varied among years due to environmental conditions. Timing of glyphosate was critical relative to weed emergence and determined the success of the treatment in terms of optimum soybean yield and gross return. Soybean yield and gross return approximated that the critical period for weed control in glyphosate-resistant no-till soybean was the unifoliolate to the one- to three-trifoliolate stage. Sequential applications of glyphosate provided higher soybean yield and gross return than a single preplant application of glyphosate. Glyphosate applied preplant or at the unifoliolate stage followed by a second application at the one- to three-trifoliolate stage consistently provided maximum average soybean yield and gross return. Gross return of the sequential glyphosate treatments was also more consistent across variable soybean price scenarios. Competition from uncontrolled later emerging weeds resulted in soybean yield loss with the single preplant application of glyphosate. Competition from uncontrolled early-emerging weeds reduced soybean yields when glyphosate was applied only at the one- to three-trifoliolate stage of soybean. Overall, two weed control strategies were identified: (1) two applications of glyphosate, the first at preplant to the unifoliolate stage, followed by a second application at the one- to three-trifoliolate stage of soybean, (b) first application of glyphosate at the unifoliolate stage followed by a second application at the one- to three-trifoliolate stage of soybean if later emerging weeds exceeded threshold densities.