Blister blight caused by obligate biotrophic pathogen Exobasidium vexans is a prevalent foliar disease in tea plants that results in significant losses in both yield and quality. To further understand the response mechanism of tea plants against E. vexans infection, transcriptomics and targeted hormone metabonomics were performed to investigate the gene expression and phytohormone signaling networks. Transcriptome analysis revealed that the most of differentially expressed genes (DEGs) were highly enriched in the pathways of “photosynthesis-antenna proteins”, “plant hormone signal transduction”, “plant-pathogen interaction”, “MAPK signaling pathway-plant”, and “phenylpropanoid biosynthesis”. The majority of disease resistance (R) genes (e.g., CDPK, PIK1, and PRS4) were activated in response to pathogen invasion in the fungal PAMP related pathway. The activation of infectioninduced genes corresponds to transcription factors such as WRKY, MYB, bHLH and AP2/ERF. SA acted as a crucial role in defense activation of tea immunity against E. vexans infection, which substances (SA and SAG) were positively correlated with the expression levels of disease-resistant genes (NPR1, TGA, and PR1) in the SA signaling pathway. The biosynthesis of defense-associated hormone metabolites such as JA, ETH, and BRs might be involved in associated with the defense response of tea plants to E. vexans infection. The correlation analysis of DEGs and hormone metabolites exhibited that JA and JA-ILE were positively regulated by the DEGs (e.g., BSK, ERF1/2, ETR, SAUR, and DELLA), suggesting JA- and BR-, ETH-, AUX-signaling might synergistically activate the expression of some defense-related genes. This finding was further validated through quantitative real-time PCR, which displayed the involvement of defense-related gene expressions in the response of tea plant to the infection caused by E. vexans. Collectively, this study provides comprehensive insights into the response mechanism of tea defense against blister blight disease to act as a valuable resource for understanding plant immunity against diverse pathogen infection and other biotic stresses in tea plants.