AbstractField experiments were conducted over 2 yr (2019 to 2020) at two locations in Iowa to evaluate multi-tactic strategies for managing multiple herbicide–resistant (MHR) waterhemp [Amaranthus tuberculatus (Moq.) Sauer] in a corn (Zea mays L.)–soybean [Glycine max (L.) Merr.] rotation. The effect of three herbicide programs on A. tuberculatus control was tested in corn (2019). The effects of the prior year’s corn weed control, a cereal rye (Secale cereale L.) cover crop, and soybean row spacing (38-cm vs. 76-cm wide) on A. tuberculatus density, biomass, and seed production were tested in soybean (2020). A herbicide program used in corn with two sites of action provided only 35% control of MHR A. tuberculatus compared with ≥97% control by a herbicide program with three sites of action. In soybean, adequate control of A. tuberculatus (≥90%) in the prior year’s corn crop and use of a cover crop or narrow rows reduced A. tuberculatus density by more than 60% at 3 and 9 wk after planting (WAP) compared with inadequate control (30%) in the prior year’s corn and no cover crop. Cover crop and narrow-row soybean reduced A. tuberculatus density by 44% at 3 WAP compared with no cover crop and wide-row soybean. Inclusion of a single control tactic, adequate control (≥90%) with multiple herbicides in the prior year’s corn, use of a cover crop, or narrow-row soybean reduced A. tuberculatus biomass and seed production at soybean harvest by at least 24% compared with inadequate control (30%) in the prior year’s corn, no cover crop, and wide-row soybean. The combination of all three control tactics reduced A. tuberculatus biomass and seed production at soybean harvest by at least 80%. In conclusion, diverse control tactics targeting A. tuberculatus at multiple life-cycle stages can make substantial contributions to the management of MHR populations.