White rot, caused by Coniella vitis, is a devastating disease in grapevine (Vitis vinifera) that seriously affects yield and quality. Breeding resistant grapevine varieties is a highly economical, environmentally friendly, and effective strategy to protect against the disease; however, this strategy requires a comprehensive understanding of the genes and pathways related to resistance. In this study, we sequenced the transcriptome of V. vinifera L. cv. GF, a highly resistant variety, at six time points after C. vitis inoculation. A transcriptome analysis showed that the salicylic acid (SA) signaling pathway was activated in response to C. vitis. Transient silencing of the VvTGA8 gene in the cv. GF greatly increased susceptibility to C. vitis. Subcellular localization studies showed that the VvTGA8 gene is localized in the nucleus. Heterologous expression of VvTGA8 in Solanum lycopersicum improved resistance to C. vitis and increased levels of the SA signaling pathway marker genes SlPR1 and SlPR2 significantly. To explore the mechanism by which VvTGA8 mediates disease resistance, we silenced SlICS1, a key gene in the SA synthesis pathway, through virus-induced gene silencing to inhibit SA synthesis in a VvTGA8 overexpression line, resulting in significantly weakened resistance to C. vitis and decreased expression levels of SlPR1 and SlPR2. We conclude that VvTGA8 is involved in SA signaling pathway, which activates the expression of pathogenesis-related genes in the nucleus, thereby mediating resistance to C. vitis in grapevine. This study provides an excellent target gene for disease-resistant breeding and gene editing in grapevine.