Trifludimoxazin is a new PPO-inhibiting herbicide that is being evaluated for the control of small-seeded annual broadleaf weeds and grasses in several crops. Currently, no information is available regarding peanut cultivar response to trifludimoxazin and its utility in peanut weed control systems. Three unique field experiments were conducted and replicated in time from 2019 through 2022 to determine the response of seven peanut cultivars (AU-NPL 17; FloRun 331; GA-06G; GA-16HO; GA-18RU; GA-20VHO; and TifNV High O/L) to preemergence (PRE) applications of trifludimoxazin and to determine the efficacy of trifludimoxazin at multiple rates and tank-mixtures with acetochlor, diclosulam, dimethenamid-P, pendimethalin, and S-metolachlor for weed management. Cultivar sensitivities to trifludimoxazin were not observed. Peanut density was not reduced by any trifludimoxazin rate. Trifludimoxazin at 75 g ai ha-1 increased leaf necrosis by 18%, peanut stunting by 10%, and reduced yield by 6% when compared to the non-treated control in 2019. However, this rate only increased leaf necrosis by 4%, stunting by 3% to 5%, and had no negative impact on yield in 2020-2021. Generally, peanut injury from PRE applied trifludimoxazin was similar to or less than that observed from flumioxazin at 2 wk after application (WAA). Peanut yield in the weed control study was reduced 11 to 12% when treated with trifludimoxazin at 150 g ha-1 rate (4X) when compared to the 75 g ha-1 rate. However, yield was not different from the flumioxazin treatment. Palmer amaranth control with trifludimoxazin systems was ≥ 91% at 13 WAA, wild radish control was ≥ 96% at 5 WAA, and annual grass control was ≥ 97% at 13 WAA. Peanut is sufficiently tolerant of 38 g ha-1 of trifludimoxazin and when tank-mixed with other residual herbicides provides weed control similar to flumioxazin-based systems.