Giant ragweed (Ambrosia trifida L.) and waterhemp (Amaranthus tuberculatus [Moq.] J.D.Sauer) are highly competitive and the most troublesome weeds in corn (Zea mays L.) and soybean (Glycine max Merr.) cropping systems in Wisconsin. Field experiments were conducted to evaluate the efficacy of multiple foliar-applied POSTemergence herbicides on giant ragweed at Janesville, WI (2020 and 2021), and on groups 2-and 9-resistant waterhemp at Brooklyn, WI (2019 and 2020), respectively.Several herbicides from site of action groups 2, 4, 5, 6, 9, 10, 14, and 27 were evaluated. Herbicide treatments were applied when giant ragweed and waterhemp reached ~10 cm in height. Herbicide efficacy (0-100% visual control) was evaluated 14 days after treatment (DAT). Group 2 herbicides provided poor (<45%) control of giant ragweed and waterhemp 14 DAT. Several herbicides encompassing different sites of action provided >90% giant ragweed control. Certain herbicides from groups 4, 10, 14, and 27 provided the best control (74-87%) of waterhemp, but no herbicide evaluated in this study provided = 90% waterhemp control. Weed management programs containing multiple effective herbicide sites of action PRE-and POST-emergence accompanied by non-chemical strategies are recommended to extend the spectrum of chemical control and reduce the risk of selection of further herbicide-resistant biotypes for both giant ragweed and waterhemp in Wisconsin and beyond.Giant ragweed (Ambrosia trifida L.) and waterhemp (Amaranthus tuberculatus [Moq.] J.D. Sauer) are highly competitive weeds in corn (Zea mays L.) and soybean (Glycine max Merr.) cropping systems (Ganie & Jhala, 2017;Wu & Owen, 2014). There are 22 (groups 2 and 9) unique cases of giant ragweed and 62 (groups 2, 4, 5, 9, 14, and 27) unique cases of waterhemp accessions with either single or multiple herbicide resistance reported in the United States (Heap, 2022). A survey of Wisconsin growers from 54 counties documented these two species as the most troublesome agricultural weeds across the state (Werle & Oliveira, 2018). A broad range of herbi-This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.