The genotype of the plant determines, through the expression of the phenotype, how well it is suited as food for herbivores. Since hybridization often results in profound genomic alterations with subsequent changes in phenotypic traits, it has the potential to significantly affect plant-herbivore interactions. In this study, we used a population of F2 hybrids that originated from a cross between a Salix viminalis and a Salix dasyclados genotype, which differed in both phenolic content and resistance to the herbivorous leaf beetle Phratora vulgatissima. We screened for plants that showed a great variability in leaf beetle performance (i.e., oviposition and survival). By correlating leaf phenolics to the response of the herbivores, we evaluated the importance of different phenolic compounds for Salix resistance to the targeted insect species. The performance of P. vulgatissima varied among the F2 hybrids, and two patterns of resistance emerged: leaf beetle oviposition was intermediate on the F2 hybrids compared to the parental genotypes, whereas leaf beetle survival demonstrated similarities to one of the parents. The findings indicate that these life history traits are controlled by different resistance mechanisms that are inherited differently in the hybrids. Salicylates and a methylated luteolin derivative seem to play major roles in hybrid resistance to Phratora vulgatissima. Synergistic effects of these compounds, as well as potential threshold concentrations, are plausible. In addition, we found considerable variation in both distributions and concentrations of different phenolics in the F2 hybrids. The phenolic profiles of parental genotypes and F2 hybrids differed significantly (e.g., novel compounds appeared in the hybrids) suggesting genomic alterations with subsequent changes in biosynthetic pathways in the hybrids.