Glyphosate resistance in weed species has presented immense challenges for farmers in Ontario. The co-application of burndown plus residual herbicides provides control of glyphosate-resistant (GR) horseweed in soybean. Pyraflufen-ethyl/2,4-D is a premixed herbicide formulation sold under the tradename Blackhawk®. Five field experiments were conducted over a 2-yr period (2019, 2020) in fields in southwestern Ontario to ascertain the biologically effective dose of pyraflufen-ethyl/2,4-D, applied alone, or mixed with metribuzin, for GR horseweed control when applied preplant to soybean. Soybean visible injury for all treatments was <15%. At 8 wk after application (WAA), the calculated doses of pyraflufen-ethyl/2,4-D for 50%, 80%, and 95% control of GR horseweed were 390, 1,148, and >2,108 g ha−1, respectively. The addition of metribuzin to pyraflufen-ethyl/2,4-D reduced the doses of pyraflufen-ethyl/2,4-D for 50%, 80%, and 95% control of GR horseweed to 19, 46, and 201 g ha−1, respectively. Pyraflufen-ethyl/2,4-D + metribuzin controlled GR horseweed by 97%, which is comparable to the current industry standards. Based on these results, pyraflufen-ethyl/2,4-D + metribuzin (527 + 400 g ha−1) applied preplant can be used for GR horseweed control in soybean.