Bayer CropScience anticipates launching several premixtures for use in soybean, targeted at control of Palmer amaranth. One of the premixtures will contain diflufenican (WSSA Group 12), metribuzin (Group 5), and flufenacet (Group 15) (DFF-containing premixture), offering an alternative site of action for soybean producers. Field experiments were conducted in Arkansas and Michigan to evaluate application timings of the DFF-containing premixture for soybean tolerance and weed control and possible cultivar tolerance differences to diflufenican and the DFF-containing premixture. Soybean injury from the 1X and 2X rates of the DFF-containing premixture ranged from 0% to 60% 14 d after planting (DAP), with injury increasing the closer the herbicide was applied to soybean emergence. Excluding the 2X rate applied 3 DAP in Arkansas in 2023, soybean injury was <20% regardless of location, site year, application timing, and rate. For weed control experiments, only a 1X rate of the DFF-containing premixture was applied at the various application timings. Control of five weed species, encompassing broadleaves and grasses, ranged from 81% to 98%, regardless of application timing by 28 DAP. By 42 DAP, weed control ranged from 71% to 97%, with the 14-d preplant application timing typically being the least effective. The DFF-containing premixture and diflufenican alone were applied PRE at 1X and 2X rates for the soybean cultivar study. Soybean metribuzin sensitivity did not affect the degree of crop response, even on a high pH soil, and injury to soybean never exceeded 20%. Overall, the DFF-containing premixture will be a tool that soybean producers can integrate into a season-long herbicide program for use across the United States regardless of the soybean cultivar.