Background: The auxin herbicides 2,4-D and dicamba are commonly used for management of horseweed (Erigeron canadensis L, (syn: Conyza canadensis L)). Halauxifen-methyl is a new auxin herbicide and recently commercialized to control several broadleaf weed species under a range of sites and environmental conditions. While synthetic auxin herbicides have been used for over 70 years, the precise mode of action that leads to plant death has yet to be clearly characterized. As new chemical families are discovered and the use of these herbicides continues to increase, it is imperative to understand how synthetic auxin active ingredients work within the plant to cause an herbicidal effect. Results: At 1 hour after treatment (HAT), 48 genes were consistently upregulated across the three herbicides, many of which are involved in the auxin-activated signaling pathway and response to auxin. At 6 HAT, 735 genes were upregulated by all herbicide treatments including genes associated with hormone signaling, metabolism, transport, senescence, and gene expression. The GO terms representing the 501 genes downregulated in all herbicide treatments were broadly categorized under two major groups: ATP and photosynthesis. At 6 HAT, over 50% of the genes differential expressed among the three herbicide treatments were unique to a single active ingredient. Conclusion: This research presents a first look into the differential gene expression profiles in horseweed following a foliar application of synthetic auxin compounds that represent three unique chemical families. While there are an abundance of transcriptome similarities induced by each herbicide that accounts for the general auxin herbicide response, distinct gene expression changes exclusive to each compound cannot be ignored as a contributor to the mode of action. Overall design: Effects of 2,4-D, dicamba, and halauxifen-methyl on horseweed (Erigeron canadensis L.)