Background and aims Allelopathy is frequently invoked as being important for successful invasion by non-native plants. Yet, the effects of specific phytochemicals of invasive plants on soil microbes remain unexplored. Methods Here we used manipulative experiments and next generation sequencing (NGS) approaches to investigate how the sesquiterpene lactones (STLs) of invasive Mikania micrantha influence soil microbial communities and nutrients.Results We found Mikania STLs to significantly increase the regulation of soil microbial activity (i.e. increased CO2 concentrations). Using the specific STL, dihydromikanolide, we found available soil nutrients to increase in the presence of this phytochemical and that bacterial richness increased while fungal richness decreased. The presence of dihydromikanolide also increased the abundance of beneficial soil bacteria and fungi associated with nutrient cycling and supply, while simultaneously lowering pathogen abundance. Clustering analysis found bacterial functional groups, such as those involved in carbon, nitrogen, phosphorus, and sulfur metabolism, to be similar in experimentally-treated dihydromikanolide soils and Mikania-invaded soils collected from the field, but significantly higher than those in uninvaded soils. This suggests that M. micrantha can enhance certain bacterial functional groups via its phytochemicals. Soil fungi, on the other hand, appeared to be less sensitive to dihydromikanolide than bacteria. Conclusions We conclude Mikania STLs, and in particular dihydromikanolide, may be key factors in determining soil microbial structure and function and may contribute to the invasion success of the species. Our findings provided a new perspective for understanding the effects of invasive plants on soil microbial communities via their impacts through phytochemicals.