Seven resistant varieties of sweetpotato were compared with three susceptible varieties in field trials and laboratory bioassays and showed that resistance was an active process rather than an escape mechanism, as field resistant varieties also had reduced root damage and oviposition compared with susceptible varieties in the laboratory. Liquid chromatography-mass spectrometry (LC-MS) of root surface and epidermal extracts showed significant variation in the concentration of hexadecyl, heptadecyl, octadecyl, and quinic acid esters of caffeic and coumaric acid, with higher concentrations correlated with resistance. All compounds were synthesized to enable their positive identification. Octadecyl coumarate and octadecyl caffeate applied to the surface of susceptible varieties in laboratory bioassays reduced feeding and oviposition, as observed on roots of resistant varieties, and therefore are implicated in weevil resistance. Segregating populations from breeding programs can use these compounds to identify trait loci for resistance and enable the development of resistant varieties.