Thirty field trials were conducted over a two-year period (2017 and 2018) at five locations to evaluate the interactions of three rates of isoxaflutole + metribuzin, the efficacy of one-, two-, and three-way herbicide tank-mixtures, and one- and two-pass herbicide programs on ten annual broadleaf and grass weed species in isoxaflutole-resistant soybean. The co-application of isoxaflutole + metribuzin provided similar or greater control of all weed species compared to the herbicides applied alone. Isoxaflutole + metribuzin had additive or synergistic control of weed species evaluated. The addition of a soil applied grass herbicide to isoxaflutole + metribuzin did not improve weed control compared to isoxaflutole + metribuzin. Isoxaflutole + metribuzin followed by glyphosate provided 98-100% control of weed species evaluated. Weed control efficacy of herbicides applied preemergence was influenced by rainfall after application. Annual weeds can be effectively controlled in isoxaflutole-resistant soybean using multiple different weed management strategies.