Gray blight disease stands as one of the most destructive ailments affecting tea plants, causing significant damage and productivity losses. However, the dynamic roles of defense genes during the infection of gray blight disease remain largely unclear, particularly concerning their distinct responses in resistant and susceptible cultivars. In the pursuit of understanding the molecular interactions associated with gray blight disease in tea plants, a transcriptome analysis unveiled that 10,524, 17,863, and 15,178 genes exhibited differential expression in the resistant tea cultivar (Yingshuang), while 14,891, 14,733, and 12,184 genes showed differential expression in the susceptible tea cultivar (Longjing 43) at 8, 24, and 72 h post-inoculation (hpi), respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted that the most up-regulated genes were mainly involved in secondary metabolism, photosynthesis, oxidative phosphorylation, and ribosome pathways. Furthermore, plant hormone signal transduction and flavonoid biosynthesis were specifically expressed in resistant and susceptible tea cultivars, respectively. These findings provide a more comprehensive understanding of the molecular mechanisms underlying tea plant immunity against gray blight disease.