Diversity is key for sustainable weed management and can be achieved via both chemical and non-chemical control tactics. Genetically modified crops with two-way or three-way stacked herbicide-tolerant traits allow use of herbicide mixtures which would otherwise be phytotoxic to the crop. Early Weed Management (EWM) strategies promote the use of preemergence (PRE) herbicides with residual activity to keep the field free of weeds early in the season for successful crop establishment. In order to evaluate the respective sustainability and practicality of the two chemical-based management tactics (i.e. stacked traits and EWM), we used a population model of waterhemp, Amaranthus tuberculatus (Moq.) Sauer (syn. rudis), to simulate the evolution of resistance in this key weed species in Midwestern U.S. soybean [Glycine max (L.) Merr.] agroecosystems. The model tested scenarios with a varying number of herbicide sites of action (SOAs), application timings (PRE and POST) and pre-existing levels of resistance. Results showed that both tactics provided opportunity for controlling resistant A. tuberculatus populations. In general, each pass over the field should include at least two effective herbicide SOAs. Nevertheless, the potential evolution of cross-resistance may void the weed-control programs embraced by stacked traits and diverse herbicide SOAs. Economic calculations suggested that the diversified programs could double long-term profitability when compared to the conventional system, because of improved yield and grain quality. Ultimately, the essence of a sustainable herbicide resistance management strategy is to be proactive. Although a herbicide-dominated approach to diversifying weed management has been prevalent, the increasing presence of weed populations with multiple resistance means that finding herbicides to which weed populations are still susceptible is becoming increasingly difficult, and thus the importance of re-introducing cultural and mechanical practices to support herbicides must be recognized.