Tea is an important cash crop worldwide, and its nutritional value has led to its high economic benefits. Tea anthracnose is a common disease of tea plants that seriously affects food safety and yield and has a far-reaching impact on the sustainable development of the tea industry. In this study, phenotypic analysis and pathogenicity analysis were performed on knockout and complement strains of HTF2—the transcriptional regulator of tea anthracnose homeobox—and the pathogenic mechanism of these strains was explored via RNA-seq. The MoHox1 gene sequence of the rice blast fungus was indexed, and the anthracnose genome was searched for CfHTF2. Evolutionary analysis recently reported the affinity of HTF2 for C. fructicola and C. higginsianum. The loss of CfHTF2 slowed the vegetative growth and spore-producing capacity of C. fructicola and weakened its resistance and pathogenesis to adverse conditions. The transcriptome sequencing of wild-type N425 and CfHTF2 deletion mutants was performed, and a total of 3144 differentially expressed genes (DEGs) were obtained, 1594 of which were upregulated and 1550 of which were downregulated. GO and KEGG enrichment analyses of DEGs mainly focused on signaling pathways such as the biosynthesis of secondary metabolites. In conclusion, this study lays a foundation for further study of the pathogenic mechanism of tea anthracnose and provides a molecular basis for the analysis of the pathogenic molecular mechanism of CfHTF2.