Abstract The aim of this work was to determine the basis of resistance in a sub-Saharan sweetpotato variety, New Kawogo, to the African sweetpotato weevil Cylas puncticollis. This insect feeds on the roots, reducing quality and yield, and is the most important production constraint of sweetpotato in Africa. Laboratory bioassays were designed to determine how the performance of weevils differed on susceptible and resistant roots. Subsequently, liquid chromatography-mass spectrometry (LC-MS) analysis of the root surface and root latex identified quantitative and qualitative differences in the chemical profiles with higher levels of octadecyl and hexadecyl esters of hydroxycinnamic acids reported in the resistant variety. The compounds were synthesized to confirm their identity and incorporated into artificial diets for bioassays on C. puncticollis. High levels of mortality and developmental inhibition were recorded for larvae feeding on treated diets, and the effect was dose-dependent. Thus, in contrast to previous work on resistant African sweetpotato cultivars, resistance in New Kawogo is not only active, but is quantifiable and manageable for breeding. Work is underway to determine what effect these compounds have on the weevils at a molecular level. The inheritance of the root latex esters will be studied in new crosses and mapped in new populations using quantitative trait loci (QTLs) that are currently being developed.