Continuous cropping obstacles seriously constrained the sustainable development of the ginseng industry. The allelopathic autotoxicity of ginsenosides is the key “trigger” of continuous cropping obstacles in ginseng. During harvest, the ginseng plants could be broken and remain in the soil. The decomposition of ginseng residue in soil is one of the important release ways of ginsenosides. Therefore, the allelopathic mechanism of ginsenosides through the decomposed release pathway needs an in-depth study. To investigate this allelopathic regulation mechanism, the integrated analysis of transcriptomics and metabolomics was applied. The prototype ginsenosides in ginseng were detected converse to rare ginsenosides during decomposition. The rare ginsenosides caused more serious damage to ginseng hairy root cells and inhibited the growth of ginseng hairy roots more significantly. By high-throughput RNA sequencing gene transcriptomics study, the significantly differential expressed genes (DEGs) were obtained under prototype and rare ginsenoside interventions. These DEGs were mainly enriched in the biosynthesis of secondary metabolites and metabolic pathways, phytohormone signal transduction, and protein processing in endoplasmic reticulum pathways. Based on the functional enrichment of DEGs, the targeted metabolomics analysis based on UPLC-MS/MS determination was applied to screen endogenous differential metabolized phytohormones (DMPs). The influence of prototype and rare ginsenosides on the accumulation of endogenous phytohormones was studied. These were mainly involved in the biosynthesis of diterpenoid, zeatin, and secondary metabolites, phytohormone signal transduction, and metabolic pathways. After integrating the transcriptomics and metabolomics analysis, ginsenosides could regulate the genes in phytohormone signaling pathways to influence the accumulation of JA, ABA, and SA. The conclusion was that the prototype ginsenosides were converted into rare ginsenosides by ginseng decomposition and released into the soil, which aggravated its allelopathic autotoxicity. The allelopathic mechanism was to intervene in the response regulation of genes related to the metabolic accumulation of endogenous phytohormones in ginseng. This result provides a reference for the in-depth study of continuous cropping obstacles of ginseng.