Populations of glyphosate-resistant (GR) Canada fleabane and GR giant ragweed can be found in several locations in southwestern Ontario. While these species can be managed individually, a scenario has developed where both species are present in GR soybean. Ten separate field experiments (five with Canada fleabane and five with giant ragweed) were conducted over a 2-yr period (2013-2014) in soybean to evaluate preplant (PP) herbicide tank mixtures that could control both weed species if they were present in the same field. Herbicides were rated for soybean injury, weed control, population density, and aboveground biomass. Two- and three-way tank mixtures containing amitrole (i.e., glyphosate amitrole, glyphosate amitrole saflufenacil, and glyphosate amitrole 2,4-D) were among the most effective treatments. For example, control of GR Canada fleabane and GR giant ragweed was at least 92% at 4 wk after treatment (WAT) and weed density and biomass were generally similar to the weed-free control. However, without amitrole, the best PP herbicide option was a three-way tank mixture of glyphosate saflufenacil 2,4-D which provided improved control and greater reductions in density and biomass compared with the two-way glyphosate tank mixtures containing saflufenacil or 2,4-D.