Grapevine (Vitis) is the world’s most valuable fruit crop, therefore, reducing yield losses to stressors is paramount. Vitis labrusca, a wild North American grapevine, is well adapted to its local environment, exhibiting stout pathogen resistance. Meanwhile, Vitis vinifera grapevine, grown worldwide for winemaking, is native to Europe and is highly susceptible to biotic stressors, particularly fungal and insect pests. V. labrusca has been long utilized in Vitis breeding programs to imbue resistance. Therefore, in this dissertation, we determined if V. labrusca acc. ‘GREM4’ was more insect herbivory resistant than V. vinifera cv. ‘PN40024’ and investigated the morphological, genetic, and metabolomic factors which may contribute to resistance. In an herbivory choice assay, Japanese beetles (Popillia japonica), a major pest of grapevine, preferred to feed upon ‘PN40024’ compared to ‘GREM4’. Further, increased leaf area was consumed on ‘PN40024’ compared to ‘GREM4’ in a time course (30min, 1h, and 4h) feeding assay. These results reported ‘GREM4’ is resistant to Japanese beetle herbivory compared to ‘PN40024’. To determine morphological adaptations that may impact defense, trichomes were next investigated. Trichome densities were greater on ‘GREM4’ compared to ‘PN40024’ leaves. In trichome-focused herbivory studies, beetles exhibited a preference for lower trichome density sides of leaves and, when provided tissues with equal trichome densities for both ‘GREM4’ and ‘PN40024’, more leaf tissue was still lost from ‘PN40024’ compared to ‘GREM4’. These results report that trichomes play a role in resistance but are not the sole factor. Therefore, we conducted a comparative transcriptomic analysis to identify differences in gene expression upon insect herbivory between the two species. When comparing constitutive expression differences prior to insect herbivory, genes with greater expression in ‘GREM4’ were enriched in secondary metabolite biosynthesis while enrichment in genes related to plant-pathogen interactions were identified in both species. Upon insect herbivory, the number of significantly differentially expressed genes (DEGs) was lowest in ‘GREM4’ at 30min and highest at 4h while the opposite was observed in ‘PN40024’. By 4h, many defense-related DEGs were identified in ‘GREM4’ compared to relatively few in ‘PN40024’. Systemic responses revealed a greater number of DEGs related to defense and signaling in ‘GREM4’ compared to ‘PN40024’. In both herbivory and systemic responses, flavonoid, phenylpropanoid, acyltransferase, and signaling-pathway genes were identified in greater numbers, or exclusively, in ‘GREM4’ compared to ‘PN40024’. To determine the impact of these transcriptomic alterations on metabolite levels, a comparative untargeted metabolomic study was conducted. Constitutively higher levels of metabolites, such as flavonoids, phenylpropanoids, and terpenes, were identified in ‘GREM4’ compared to ‘PN40024’ leaves while, after 1h of herbivory, a greater number of significantly differentially accumulating metabolites (DAMs) were identified in ‘PN40024’ compared to ‘GREM4’. Constitutively and inducibly increased levels of metabolites with insect repellent and insecticidal properties were observed in ‘GREM4’ compared to ‘PN40024’. Candidate genes and metabolites reported may be employed in future functional studies to determine their impact on resistance. Findings presented herein will inform research endeavors to increase insect herbivory resistance of Vitis, and likely other crops.