Because of the increasing number of glyphosate-resistant weeds, alternate herbicide-resistant crops and herbicides with different modes of action are required to protect crop yield. Glufosinate is a broad-spectrum POST herbicide for weed control in glufosinate-resistant crops, including soybean. The objective of this study was to compare herbicide programs with glufosinate applied singly at late-POST (LPOST) or sequentially at early POST (EPOST) followed by (fb) LPOST applications and PRE herbicides fb EPOST/LPOST glufosinate alone or tank-mixed with acetochlor, pyroxasulfone, or S-metolachlor in glufosinate-resistant soybean. A field experiment was conducted at the South Central Agriculture Laboratory in Clay Center, NE, in 2012 and 2013. Glufosinate applied in a single LPOST or sequential EPOST fb LPOST application controlled common lambsquarters, common waterhemp, eastern black nightshade, green foxtail, large crabgrass, and velvetleaf ≤ 82% and resulted in a weed density of 6 to 10 plants m−2 by the end of the season. Flumioxazin-, saflufenacil-, or sulfentrazone-based premixes provided 84 to 99% control of broadleaf and grass weeds tested in this study at 15 d after PRE application and a subsequent LPOST application of glufosinate alone controlled broadleaf and grass weeds 69 to 93% at harvest, depending on the herbicide program and weed species being investigated. The PRE application of sulfentrazone plus metribuzin fb EPOST glufosinate tank-mixed with acetochlor, pyroxasulfone, or S-metolachlor controlled the tested broadleaf and grass weeds ≥ 90%, reduced density to ≤ 2 plants m−2, and reduced weed biomass to ≤ 10 g m−2 and produced soybean yields of ≥ 4,450 and 3,040 kg ha−1 in 2012 and 2013, respectively. Soybean injury was 0 to 20% from PRE or POST herbicides, or both and was inconsistent, but transient, during the 2-yr study, and it did not affect soybean yield. Sulfentrazone plus metribuzin applied PRE fb glufosinate EPOST tank-mixed with acetochlor, pyroxasulfone, or S-metolachlor provided the highest level of weed control throughout the growing season and increased soybean yield compared with a single LPOST or a sequential EPOST fb LPOST glufosinate application. Additionally, these herbicide programs provide four distinct mechanisms of action that constitute an effective weed-resistance management strategy in glufosinate-resistant soybean.