Field and greenhouse experiments were conducted to characterize the response of a waterhemp population from McLean County, IL to foliar-applied 4-hydroxyphenylpyruvate dioxygenase (HPPD) –inhibiting herbicides and determine the population's sensitivity to herbicides from other site-of-action groups. In the field, 10 to 15–cm-tall waterhemp treated with mesotrione at 105 g ai ha−1, tembotrione at 92 g ai ha−1, or topromezone at 18 g ai ha−1 had significantly greater biomass (≥ 10%) 14 d after treatment (DAT) than waterhemp harvested the day of herbicide application, indicating growth had occurred following herbicide application. Waterhemp growth stage at the time of herbicide application influenced control. Mesotrione applied at 105 g ha−1 alone or combined with atrazine at 560 g ai ha−1 provided significantly greater waterhemp control (≥ 66%) when applied to small waterhemp plants (2 to 5 cm tall) compared with applications made to plants 5 to 10 or 10 to 15 cm tall. Glyphosate, glufosinate, fomesafen, lactofen, or acifluorfen provided greater waterhemp control (≥ 68%) 7 and 14 DAT than mesotrione, dicamba, or 2,4-D. Control of this population with atrazine, chlorimuron, and imazethapyr did not exceed 12%. Results of a greenhouse experiment with waterhemp plants grown from field-collected seed were similar to field data, and confirm the McLean County population was poorly controlled with HPPD, photosystem II, and acetolactate synthase inhibitors.