Downy brome is a cleistogamous facultative winter-annual grass weed that invades cropland, pastureland, and ruderal areas in western North America. Glyphosate-resistant downy brome, the first known glyphosate-resistant grass weed in Canada, was confirmed in a glyphosate-resistant canola field in southern Alberta in 2021. A controlled-environment study was conducted to determine the impact of preemergence soil-applied residual herbicides on glyphosate-resistant and susceptible downy brome in two field soils. Flumioxazin/pyroxasulfone (70/89 g ai ha−1), carfentrazone/pyroxasulfone (18/150 g ai ha−1), sulfentrazone/pyroxasulfone (100/100 or 150/150 g ai ha−1), and saflufenacil/pyroxasulfone (36/120 g ai ha−1) resulted in excellent (≥90%) visible control and downy brome biomass reduction 8 wk after treatment (WAT). The low rate of carfentrazone/pyroxasulfone (12/100 g ai ha−1) resulted in good (≥80%) visible control and biomass reduction 8 WAT, while the low and medium rates of saflufenacil/pyroxasulfone (18/60 or 25/84 g ai ha−1) resulted in ≥80% biomass reduction but suppression only (66% to 75%) based on visible control. Flumioxazin alone (105 g ai ha−1) resulted in good visible control (81%) 8 WAT in a sandy loam soil, but poor (13%) control in a clay loam soil. Soil type affected plant growth as evidenced by reduced growth in the untreated sandy loam soil compared to clay loam soil. The glyphosate-resistant population emerged and grew more vigorously than the glyphosate-susceptible population resulting in greater plant densities in the untreated control and some less-effective herbicide treatments. These results suggest that mixtures of a protoporphyrinogen oxidase-inhibiting herbicide with the very-long-chain fatty acid elongase inhibitor pyroxasulfone applied preemergence at ≥89 g ai ha−1 could be effective components of an herbicide layering strategy targeting glyphosate-resistant and glyphosate-susceptible downy brome.