Herbicides that inhibit very-long-chain fatty acids (VLCFAs) have been widely used for preemergence control of annual monocot and small-seeded dicot weed species, such as waterhemp, since their discovery in the 1950s. VLCFA-inhibiting herbicides are often applied in combination with active ingredients that possess residual activity on small-seeded broadleaf weeds, which can make their contribution to preemergence waterhemp control difficult to quantify. Bare-ground field experiments were designed to investigate the efficacy of eight VLCFA-inhibiting herbicides applied at their minimum and maximum labeled rates for control of Illinois waterhemp populations. Four different locations were selected, two of which contained previously characterized VLCFA inhibitor–resistant waterhemp populations in Champaign County (CHR) and McLean County (MCR). Two locations with VLCFA inhibitor–sensitive waterhemp populations included the University of Illinois South Farm in Urbana, IL, and the Orr Research Center in Perry, IL. Soils at the CHR, MCR, and Urbana locations contained greater than 3% organic matter, but less than 3% organic matter at Perry. Non-encapsulated acetochlor and alachlor controlled CHR and MCR waterhemp populations 28 d after treatment (DAT), whereas other VLCFA-inhibiting herbicides resulted in 61% and 76% control of the CHR and MCR populations, respectively. In contrast, all VLCFA-inhibiting herbicides resulted in 81% and 88% control of the Perry and Urbana waterhemp populations, respectively, 28 DAT. Waterhemp control decreased by 42 DAT, especially for the VLCFA inhibitor–resistant CHR and MCR populations. Overall, VLCFA-inhibiting herbicides remain effective for controlling sensitive waterhemp, but most are not effective for controlling VLCFA inhibitor–resistant waterhemp populations. Proper herbicide stewardship and integrated weed management practices should be implemented to maintain VLCFA-inhibiting herbicide efficacy for waterhemp management in the future.