Grapevine (Vitis vinifera L.) is a globally significant economic crop. However, its widely cultivated varieties are highly susceptible to white rot disease. To elucidate the mechanisms of resistance in grapevine against this disease, we utilized time-ordered gene co-expression network (TO-GCN) analysis to investigate the molecular responses in the grapevine varieties ‘Guifeimeigui’ (GF) and ‘Red Globe’ (RG). An assessment of their resistance demonstrated that GF is highly resistant to white rot, whereas RG is highly susceptible. We conducted transcriptome sequencing and a TO-GCN analysis on leaf samples from GF and RG at seven time points post-infection. Although a significant portion of the differentially expressed genes related to disease resistance were shared between GF and RG, the GF variety rapidly activated its defense mechanisms through the regulation of transcription factors during the early stages of infection. Notably, the gene VvLOX3, which is a key enzyme in the jasmonic acid biosynthetic pathway, was significantly upregulated in GF. Its upstream regulator, Vitvi08g01752, encoding a HD-ZIP family transcription factor, was identified through TO-GCN and yeast one-hybrid analyses. This study provides new molecular insights into the mechanisms of grapevine disease resistance and offers a foundation for breeding strategies aimed at enhancing resistance.