To enable the future establishment of safe weevil-resistance strategies, anti-weevil metabolites from sweetpotato should be investigated. In the present study, we pretreated sweetpotato leaves with exogenous chlorogenic acid and then exposed them to sweetpotato weevils to evaluate this compound’s anti-insect activity. We found that chlorogenic acid applied to sweetpotato conferred significant resistance against sweetpotato-weevil feeding. We also observed enhanced levels of chlorogenic acid in response to weevil attack in sweetpotato leaves. To clarify how sweetpotato weevils regulate the generation of chlorogenic acid, we examined key elements of plant-herbivore interaction: continuous wounding and phytohormones participating in chlorogenic acid formation. According to our results, sweetpotato weevil-derived continuous wounding induces increases in phytohormones, including jasmonic acid, salicylic acid, and abscisic acid. These phytohormones can upregulate expression levels of genes involved in chlorogenic acid formation, such as IbPAL, IbC4H and IbHQT, thereby leading to enhanced chlorogenic acid generation. This information should contribute to understanding of the occurrence and formation of natural anti-weevil metabolites in sweetpotato in response to insect attack and provides critical targets for the future breeding of anti-weevil sweetpotato cultivars.