Intercropping or assistant endophytes promote phytoremediation capacities of hyperaccumulators and enhance their tolerance to heavy metal (HM) stress. Findings from a previous study showed that intercropping the hyperaccumulator Sonchus asper (L.) Hill grown in HM-contaminated soils with maize improved the remediating properties and indicated an excluder-to-hyperaccumulator switched mode of action towards lead. In the current study, RNA-Seq analysis was conducted on Sonchus roots grown under intercropping or monoculture systems to explore the molecular events underlying this shift in lead sequestering strategy. The findings showed that intercropping only slightly affects S. asper transcriptome but significantly affects expression of root-associated microbial genomes. Further, intercropping triggers significant reshaping of endophytic communities associated with a ‘root-to-shoot’ transition of lead sequestration and improved phytoremediation capacities of S. asper . These findings indicate that accumulator activities of a weed are partially attributed to the root-associated microbiota, and a complex network of plant–microbe-plant interactions shapes the phytoremediation potential of S. asper . Analysis showed that intercropping may significantly change the structure of root-associated communities resulting in novel remediation properties, thus providing a basis for improving phytoremediation practices to restore contaminated soils.