Greenhouse and field studies were conducted with a population of common waterhemp resistant to POST protoporphyrinogen oxidase (protox)-inhibiting herbicides to compare its response to PRE and POST applications of selected herbicides. In the greenhouse, a dose–response study of PRE applications of acifluorfen, fomesafen, or lactofen was conducted on protox-susceptible and -resistant common waterhemp. The protox-resistant biotype was approximately 6.3, 2.5, and 2.6 times more resistant than the susceptible biotype to acifluorfen, fomesafen, and lactofen, respectively. In a separate study under field conditions, protox-resistant common waterhemp were treated with PRE and POST applications of acifluorfen, azafenidin, flumioxazin, fomesafen, lactofen, oxyfluorfen, or sulfentrazone. At 14 and 28 d after POST treatment (DAPT) in 2002 and 2004, all PRE applications of herbicides gave greater control than did POST applications. At 14 DAPT, oxyfluorfen had the greatest difference in PRE and POST control, with 85 and 10% control in 2002, respectively. An additional field study was conducted to determine the stage of growth at which resistance to protox-inhibiting herbicides becomes most prevalent. Protox-resistant common waterhemp were treated with herbicides at the 2-leaf, 4- to 6-leaf, and 8- to 10-leaf growth stage. Acifluorfen and fomesafen at 420 g ha−1 gave greater than 90% control at the 2-leaf stage and 4- to 6-leaf stage, except in 2003 when control was 85% with acifluorfen. In 2003 and 2004, common waterhemp control at the 8- to 10-leaf stage ranged between 54 and 75% with acifluorfen or fomesafen. Results indicate that common waterhemp resistance to customary rates of POST protox-inhibiting herbicides becomes prevalent after the 4- to 6-leaf growth stage.