Herbicide-resistant weeds threaten modern agriculture production. In Michigan, horseweed [Erigeron canadensis L.; syn.: Conyza canadensis (L.) Cronq.] is among the most troublesome weeds, and glyphosate was widely used to control E. canadensis. Due to extreme selection pressure imposed by heavy glyphosate usage, glyphosate-resistant E. canadensis is widespread. New technologies to control resistant E. canadensis are being introduced in the form of multiple herbicide resistance traits integrated into glyphosate-resistant soybean [Glycine max (L.) Merr.] (e.g., dicamba or 2,4-D choline). These new soybean varieties will likely increase the use of 2,4-D and dicamba, thus increasing the resistance selection pressure in E. canadensis. Predicting agronomic factors that drive herbicide-resistance evolution can serve as an effective proactive tool to advise practitioners to modify management strategies. Therefore, the objectives of this study are: (1) conduct dose–response assays to assess the current resistance spectrum of E. canadensis collected in Michigan and (2) predict and determine the main factors in row-crop production that contribute to resistance evolution in these accessions. Dose–response assays were conducted to evaluate the herbicide sensitivity spectrum to glyphosate, dicamba, and 2,4-D in 20 E. canadensis accessions collected from eight Michigan counties. Out of the 20 accessions, 60% were resistant to glyphosate, 35% to 2,4-D, and 20% to dicamba. Pearson's correlation coefficient of dose–response values was positive in all comparisons (2,4-D-dicamba, r = 0.35; dicamba-glyphosate, r = 0.15; 2,4-D-glyphosate, r = 0.21). Dose–response data were integrated in odds ratio analyses to access the influence that previous management history had on the occurrence of resistance. Out of the significant pairwise comparisons, 44% were related to crop rotation frequency, 33% to previous herbicide-resistance status, and 22% to location where collected. Results highlight that growers have the ability to proactively manage herbicide-resistance evolution progression of E. canadensis in Michigan by adopting integrated weed management techniques to slow successive selection events that occur in low-diversity management systems.