Twenty field experiments were conducted from 2021-2022 at nine locations in Ontario, Canada to optimize weed control in E3 soybean. Two studies compared one- and two-pass weed control programs for control of glyphosate-resistant (GR) Canada fleabane and multiple herbicide-resistant (MHR) waterhemp. Two-pass weed control programs provided greater control of GR Canada fleabane and MHR waterhemp. Another study investigated herbicide interactions for volunteer corn control in E3 soybean. The co-application of 2,4-D choline or dicamba with quizalofop-p-ethyl or clethodim resulted in antagonistic herbicide interactions and reduced control. Glufosinate co-applied with quizalofop-p-ethyl or clethodim resulted in a synergistic interaction. The effect of glufosinate rate, the addition of AMS, and weed size at application was established for five annual weed species. The effect of glufosinate rate, the addition of AMS, and weed size at application is weed species specific. Generally, control is improved with increased rate and reduced weed size at application.