The perceived risk of pre-emergence (PRE) herbicide injury negatively affecting soybean [Glycine max (L.) Merr.] grain yield may cause growers to select herbicides and/or rates that, consequently, reduce waterhemp (Amaranthus tuberculatus (Moq.) J.D. Sauer] control. Research was conducted over 3 years with flumioxazin and sulfentrazone to evaluate the influence of herbicide rate and mixture on waterhemp control and soybean injury, density, development, and grain yield. In a year with limited rainfall, waterhemp control was >90% up to 9 weeks after planting (WAP) and soybean injury never exceeded 7% from all treatments. In years with more adequate moisture, reduced rates of either flumioxazin or sulfentrazone applied with any mixture herbicide provided similar waterhemp control (>95%) to a full-labeled rate of flumioxazin or sulfentrazone applied alone at 3 WAP. A full-labeled rate of flumioxazin or sulfentrazone in mixture with fomesafen + S-metolachlor provided the greatest and most uniform waterhemp control (>90%) at 9 WAP. When applied at full-labeled (1x) rates, soybean injury at 3 WAP from flumioxazin- and sulfentrazone-based treatments ranged from 8 to 18% and 2 to 6%, respectively. Similar trends among treatments were observed for soybean density. Despite early-season injury, treatments applied at a 1x rate did not reduce grain yield. However, applicators should be cognizant of spray boom overlap as 2x rates increased the extent of yield loss by up to 10 bu acre(-1). Soybean injury at 9 WAP was a more accurate predictor of grain yield loss (R-2 = .51) than injury at 3 WAP (R-2 = .14).