Owing to the climate change impacts, waterlogging is one of the most hazardous abiotic stresses to crops, which also can result in a serious reduction in the quantity and quality of grape berry and wine production during the rainy season. Therefore, the exploration of the response mechanism of grape to waterlogging is necessary, for which the analysis of the transcriptomic regulation networks of grapevine leaves in response to waterlogging stress was carried out. In this study, 12 634 genes were detected in both waterlogging stress and control grapevine plants, out of which 6837 genes were differentially expressed. A comparative analysis revealed that genes functioning in the antioxidant system, glycolysis and fermentation pathway, chlorophyll metabolism, amino acid metabolism and hormones were activated to reduce injury to grapes under the waterlogging stress. Meanwhile, genes encoding class-2 non-symbiotic haemoglobin were determined as important in waterlogging acclimation. Additionally, the expression variations of three marker genes were found to be informative and can be used to predict the viability of the grapevines subjected to waterlogging. This research not only probes the molecular mechanism underlying grapevine waterlogging tolerance but also puts forward an idea about the application of gene expression information to practical management.