Glyphosate-resistant (GR) Palmer amaranth is a problematic, annual broadleaf weed in soybean production fields in Nebraska and many other states in the United States. Soybean resistant to 2,4-D, glyphosate, and glufosinate (Enlist E3TM) has been developed and was first grown commercially in 2019. The objectives of this research were to evaluate the effect of herbicide programs applied PRE, PRE followed by (fb) late-POST (LPOST), and early-POST (EPOST) fb LPOST on GR Palmer amaranth control, density, and biomass reduction, soybean injury, and yield. Field experiments were conducted near Carleton, NE, in 2018, and 2019 in a grower’s field infested with GR Palmer amaranth in 2,4-D–, glyphosate-, and glufosinate-resistant soybean. Sulfentrazone + cloransulam-methyl, imazethapyr + saflufenacil + pyroxasulfone, and chlorimuron ethyl + flumioxazin + metribuzin applied PRE provided 84% to 97% control of GR Palmer amaranth compared with the nontreated control 14 d after PRE. Averaged across herbicide programs, PRE fb 2,4-D and/or glufosinate, and sequential application of 2,4-D or glufosinate applied EPOST fb LPOST resulted in 92% and 88% control of GR Palmer amaranth, respectively, compared with 62% control with PRE-only programs 14 d after LPOST. Reductions in Palmer amaranth biomass followed the same trend; however, Palmer amaranth density was reduced 98% in EPOST fb LPOST programs compared with 91% reduction in PRE fb LPOST and 76% reduction in PRE-only programs. PRE fb LPOST and EPOST fb LPOST programs resulted in an average soybean yield of 4,478 and 4,706 kg ha−1, respectively, compared with 3,043 kg ha−1 in PRE-only programs. Herbicide programs evaluated in this study resulted in no soybean injury. The results of this research illustrate that herbicide programs are available for the management of GR Palmer amaranth in 2,4-D–, glyphosate-, and glufosinate-resistant soybean.