Background: In Traditional Chinese Medicine (TCM), the heads and tails of Angelica sinensis (Oliv.) Diels (AS) is used in treating different diseases due to their different pharmaceutical efficacies. The underline mechanisms, however, have not been fully explored. Objective: Novel mechanisms responsible for the discrepant activities between AS heads and tails were explored by a combined strategy of transcriptomes and metabolomics. Method:: Six pairs of the heads and tails of AS roots were collected in Min County, China. Total RNA and metabolites, which were used for RNA-seq and untargeted metabolomics analysis, were respectively isolated from each AS sample (0.1 g) by Trizol and methanol reagent. Subsequently, differentially expressed genes (DEGs) and discrepant pharmaceutical metabolites were identified for comparing AS heads and tails. Key DEGs and metabolites were quantified by qRT-PCR and targeted metabolomics experiment. Results: Comprehensive analysis of transcriptomes and metabolomics results suggested that five KEGG pathways with significant differences included 57 DEGs. Especially, fourteen DEGs and six key metabolites were related to the metabolic regulation of Phenylpropanoid biosynthesis (PB) pathway. Results of RT-qPCR and targeted metabolomics indicated that higher levels of expression of crucial genes in PB pathway, such as PAL, CAD, COMT and peroxidase in the tail of AS, were positively correlated with levels of ferulic acid-related metabolites. The average content of ferulic acid in tails (569.58±162.39 nmol/g) was higher than those in the heads (168.73 ± 67.30 nmol/g) (P˂0.01); Caffeic acid in tails (3.82 ± 0.88 nmol/g) vs heads (1.37 ± 0.41 nmol/g) (P˂0.01), and Cinnamic acid in tails (0.24 ± 0.09 nmol/g) vs heads (0.14 ± 0.02 nmol/g) (P˂0.05). Conclusion: Our work demonstrated that overexpressed genes and accumulated metabolites derived from PB pathway might be responsible for the discrepant pharmaceutical efficacies between AS heads and tails.