Selection of effective herbicide strategies (i.e., one- versus two-pass and timing [preemergence (PRE) versus postemergence (POST)]) is of great importance to corn growers. Field studies were conducted at Arlington (2018 and 2019), Brooklyn (2019), Lancaster (2019), and Janesville (2018 and 2019), Wisconsin (six site-years) to evaluate overall end-of-season weed control efficacy of multiple herbicide strategies in conventional tillage corn production systems. Herbicide strategy treatments included one-pass PRE, one-pass POST, two-pass PRE followed by (fb) POST, and two-pass PRE fb POST with layered residual herbicides (LRPOST). The weed species present at the experimental site-years were common lambsquarters, giant foxtail, giant ragweed, velvetleaf, and/or waterhemp. Except Arlington-2019, the herbicide strategy was not as influential for the site-years infested with common lambsquarters, giant foxtail, velvetleaf, and/or waterhemp species (e.g., Arlington 2018, Brooklyn 2019, Lancaster 2019), as effective overall end-of-season control (>90%) was achieved regardless of the herbicide strategy, and no significant differences were observed in the combined weed biomass across strategies. A two-pass strategy (e.g., PRE followed by POST, or PRE followed by LRPOST) was necessary for effective overall end-of-season control at the site-years infested with giant ragweed (Janesville 2018 and 2019). Weed interference reduced corn yield by 11 to 75% across site-years. Although certain weed communities can be effectively controlled by a one-pass herbicide strategy, two-pass strategies provided the greatest and most consistent overall end-of-season weed control and corn yield across all site-years, regardless of weed species composition and environmental conditions. Hence, a two-pass herbicide strategy is recommended for Wisconsin conventional tillage corn production to ensure effective end-of-season weed control while protecting yield potential of the crop, particularly in fields infested with moderate to high density of troublesome weeds such as giant ragweed.