Two experiments were conducted in 2013 and 2014 in Florida to evaluate the effects of protoporphyrinogen oxidase (PPO)-inhibiting herbicides and single versus sequential applications on Palmer amaranth control and peanut injury. Protoporphyrinogen oxidase-inhibiting herbicides are among the last available herbicides for the POST control of acetolactate synthase (ALS)-resistant Palmer amaranth in peanut. Lactofen (219 g ai ha–1) applied 5 d after the initial application provided the highest level of Palmer amaranth control 7 and 14 d after initial application (DAIT). Delaying sequential applications of lactofen to 15 d resulted in the highest level of Palmer amaranth control 21 and 28 DAIT. Similar to Palmer amaranth control, foliar injury to peanut was often highest from lactofen applications, and by 28 DAIT lactofen treatments were the only treatments that caused foliar injury. Although no statistical difference was observed between yields of plots treated with acifluorfen (280 g ai ha–1), bentazon (560 g ai ha–1), 2,4-DB (280 g ae ha–1) alone or in combination with each other, plots treated with sequential applications of lactofen 5 or 15 DAIT produced the lowest yields. Sequential applications of lactofen applied 15 DAIT controlled Palmer amaranth more effectively than any other treatment but also caused the highest level of peanut injury. The use of sequential applications of lactofen was the most effective method for control of Palmer amaranth in this study, but did reduce peanut yield.