Echinacea purpurea (L.) Moench is an important medicinal plant with a wide range of therapeutic potentials that is extensively applied in pharmaceutical industry. The molecular bases and regulatory mechanisms of active compounds in E. purpurea, are yet to be fully described. In the study, to explore genome-wide transcriptional and metabolic changes, seedlings elicited by methyl jasmonate (MeJA) were analyzed by integrative transcriptome sequencing and quantitative chemical profiling. The plants exposed to MeJA significantly increased accumulation of phenolic compounds content as well as phenylalanine ammonia-lyase (PAL) activity, compared with control plants. The assembly of the clean reads generated 85,736 unigenes, in which more than 52% were annotated. Transcriptome analysis revealed that MeJA induces major transcriptional changes, especially metabolic, and signal transduction pathways. Overall, 5538 differentially expressed genes were identified after MeJA application that some of them were assigned to transcription factors (TFs), protein kinases (PKs), and transporters involved in phenolic secondary metabolite biosynthesis. Moreover, core genes in the pathways of phenylalanine and phenylpropanoid were affected by MeJA. A transcriptional regulatory network from transcriptome profiles of TFs and genes involved in phenolics biosynthesis pathway were constructed that identified hub genes which might play central regulatory roles in secondary metabolite biosynthesis. The current study provides a comprehensive genomic dataset that can serve as a resource to better understanding of the phenolic biosynthesis and improveing metabolic engineering strategies for overproduction of bioactive metabolites in Echinacea industry.