Edamame, a specialty food-grade soybean popular among health-conscious consumers, is growing in popularity worldwide. Despite a well-developed soybean industry, most edamame consumed in the United States is imported from Asia. Considerable interest exists in growing edamame domestically; however, weed interference is a major problem, and until recently, only a single herbicide was registered for use on the crop. The objectives of this work were (1) to compare effectiveness of weed management treatments that utilize herbicides currently registered for use on edamame or that may be registered in the near future, (2) to determine the significance of edamame cultivar on performance of these treatments, and (3) to identify potential relationships between the crop and weed. Ten different weed management treatments were tested in three edamame cultivars over a 3-yr period. All weed management treatments increased marketable pod yield relative to the nontreated control, but only treatments with saflufenacil or S-metolachlor combinations were comparable to the hand-weeded weed-free treatment. Of the treatments studied, S-metolachlor followed by imazamox was among the greatest yielding, had the least weed density and biomass, and did not reduce crop population density. Also, cultivars differed in their weed-suppressive ability. Path analysis indicated certain relationships were consistent across cultivars, such as weed population density having a direct negative association with crop biomass; however, other edamame–weed interactions were not identical across cultivars. Although more improvements are needed, the vegetable industry is beginning to have nascent weed management options in edamame, which will likely reduce reliance on hand weeding and result in crop-production costs that are more competitive in the global market.