Field experiments were conducted at two locations in 2003 and 2004 to determine dark tobacco tolerance and weed control from postemergence over-the-top (POT) and postemergence-directed (PD) applications of trifloxysulfuron and halosulfuron. Trifloxysulfuron was applied at 3.6 or 5.3 g ai/ha and halosulfuron was applied at 36 or 53 g ai/ha. Trifloxysulfuron POT injured ‘Narrowleaf Madole’ dark tobacco 16 to 33% and halosulfuron POT caused 32 to 33% injury at 1 wk after treatment (WAT). Tobacco plant height at 1 WAT with POT applications was also reduced by up to 31% at one of two locations. Tobacco injury from POT applications had dissipated to 6 to 12% by 4 WAT. Despite extensive early-season injury, most POT herbicide applications did not significantly reduce tobacco yield, mean grade index, and gross revenue compared to tobacco that only received pretransplant applications of sulfentrazone plus clomazone. Dark tobacco was much more tolerant to PD applications of either herbicide, with no more than 4% injury observed at 1 WAT. Neither herbicide controlled horsenettle more than 57% at either application rate or method. Although trifloxysulfuron and halosulfuron could contribute to tobacco weed control programs by providing postemergence control of several common weed species, PD applications would be the only acceptable method of application due to excessive injury observed from POT applications of these herbicides.