Field experiments were performed in 2016 and 2017 in Missouri to determine whether interactions exist between PRE herbicides and seed treatments in soybean. The experiments consisted of a randomized complete block design with factorial arrangements of varieties, seed treatments, and herbicides. We selected two genetically similar varieties of soybean, one with known tolerance to PPO-inhibiting herbicides and one with known sensitivity. Each variety of seed received three separate seed treatment mixtures (STMs): (1) STM1, imidacloprid plus prothioconazol+penflufen+metalaxyl plus metalaxyl plus Bacillus subtilis+B. pumilis, (2) STM2, Pasteuria nishizawae plus thiamethoxam plus prothioconazol+penflufen+metalaxyl plus metalaxyl plus B. subtilis+B. pumilis, and (3) STM3, fluopyram plus imidacloprid plus prothioconazol+penflufen+metalaxyl plus metalaxyl plus B. subtilis+B. pumilis. Chlorimuron-ethyl+flumioxazin+pyroxasulfone, chlorimuron-ethyl+flumioxazin+metribuzin, and chlorimuron-ethyl+sulfentrazone were applied PRE to each variety and seed treatment combination at 1× and 2× the labeled use rate. Chlorimuron-ethyl+sulfentrazone treatment at the 2× rate resulted in greater injury of 8% and 14% to the sensitive variety than the tolerant in 2016 and 2017, respectively; this was the highest injury observed from any herbicide treatment in either year. In 2017, chlorimuron-ethyl+sulfentrazone resulted in the greatest height reductions in both varieties, but this reduction was more evident in the sensitive (19%) than in the tolerant (6%) variety. Overall, yield differences between the two varieties were not consistent between years, and for both varieties, the sulfentrazone-containing treatments resulted in the highest yield losses. The results of this research indicate that there is a larger interaction between herbicides and varieties than there is between herbicides and seed treatments, or seed treatments and varieties.