Pierce's disease is of major concern for grapevine (Vitis vinifera) production wherever the bacterial pathogen Xylella fastidiosa and its vectors are present. Long-term management includes the deployment of resistant grapevines such as those containing the PdR1 locus from the wild grapevine species Vitis arizonica, which do not develop Pierce's disease symptoms upon infection. However, little is understood about how the PdR1 locus functions to prevent disease symptom development. Therefore, we assessed the concentrations of plant defense-associated compounds called phenolics in healthy and X. fastidiosa-infected PdR1-resistant and susceptible grapevine siblings over time. Soluble foliar phenolic levels, especially flavonoids, in X. fastidiosa-infected PdR1-resistant grapevines were discovered to be significantly lower than those in infected susceptible grapevines. Therefore, it was hypothesized that PdR1-resistant grapevines, by possessing lowered flavonoid levels, affects biofilm formation and causes reduced X. fastidiosa intra-plant colonization, thus limiting the ability to increase pathogen populations and cause Pierce's disease. These results therefore reveal that differences in plant metabolite levels might be a component of the mechanisms that PdR1 utilizes to prevent Pierce's disease.