Herbicide-tolerant (HT) crops that are genetically engineered to withstand applications of multiple herbicidal modes of action are commonly produced in fields adjacent to flue-cured tobacco. The next generation of HT crops will express tolerance to a class of herbicides known as 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors. The impact of HPPD-inhibiting herbicide exposure to flue-cured tobacco foliage has not been reported. Research was initiated at two field sites in 2022 to measure the effects of isoxaflutole and mesotrione to cured leaf yield, quality, and value. Within each active ingredient, five sub-lethal concentrations (25, 5, 1, 0.2, and 0.1 % v/v of the full rate) were applied at two different times (five and 10 weeks after transplanting). A non-treated control was included for comparison. Visual injury was greatest when exposure occurred five weeks after transplanting, and was not apparent at the later exposure time. Within the early exposure timing, visual injury declined with sub-lethal dose, although mesotrione was generally more injurious than isoxaflutole when pairwise comparisons were made between common doses. Moreover, visual injury was difficult to identify when sub-lethal dose concentrations were less than one percent. Finally, cured leaf yield was impacted by the interaction of sub-lethal dose concentration and exposure timing, with the 5 and 25 % v/v concentrations at five weeks after transplanting yielding significantly lower than the 0.1 and 0.2 % v/v concentrations at 10 weeks after transplanting. The decline in yield translated into a decline in crop value that followed an identical trend. Cured leaf visual quality was not impacted. Our results suggest that HPPD-inhibiting herbicides pose a threat to flue-cured tobacco when exposure occurs early in the growth cycle and when the concentration exceeds 5 % v/v.