Tetflupyrolimet is a novel herbicide that inhibits dihydroorotate dehydrogenase (DHODH), interfering with de novo pyrimidine biosynthesis in susceptible plants. While tetflupyrolimet efficacy for preemergence grassy weed control in rice (Oryza sativa L.) and managed turfgrass systems has been explored, there is minimal information regarding effects that edaphic factors may have on activity, particularly those pertaining to soil hydraulics. Dose–response experiments revealed 6- to 8-fold differences in tetflupyrolimet activity on annual bluegrass (Poa annua L.) due to soil texture, with higher activity reported following applications to sand compared with clay loam. Higher tetflupyrolimet activity in sand could be related to matric potential, as activity following applications to plants growing in sand exceeded that observed on clay loam across a wide range of volumetric water contents (15% to 60%). Once volumetric water content increased to ≥ 80%, no differences in tetflupyrolimet activity were detected between soils, suggesting that post-application irrigation could mitigate potential reductions in efficacy on finer-textured soils when moisture is limited. These findings underscore that soil texture and, consequently, moisture retention affect tetflupyrolimet activity to the extent that application rates could vary based on soil texture in turfgrass systems. Further research exploring a broader range of soil types and field conditions is warranted to refine tetflupyrolimet rate recommendations based on soil type.