The effect of drought stress on the resistance of sweetpotato roots to sweetpotato weevil (SPW), Cylas formicarius (Fab.), was studied in 1997 and 1998 in two genotypes (“Beauregard” and “Excel”) with different SPW susceptibility. Storage roots produced under drought or normal conditions were tested for adult feeding, oviposition, larval survival and pupal weight in the laboratory under no-choice and free-choice test conditions. The levels of sweetpotato resin glycoside and caffeic acid in the periderm tissue of the roots were also determined. Drought-stressed roots received significantly more SPW eggs under no-choice and free-choice conditions and more feeding punctures under free-choice conditions than non-stressed roots in 1997. Larval survival rate was significantly lower on drought-stressed roots. A significant drought effect on feeding, oviposition and larval survival was absent in 1998. Drought stress had no effect on sweetpotato resin glycosides content in both years, but significantly reduced the content of caffeic acid in 1997. Genotype had a significant effect on SPW feeding in 1997 and on feeding and oviposition in 1998 under free-choice test conditions, where Beauregard was preferred for both feeding and oviposition. Beauregard also supported a significantly higher larval survival rate compared with Excel. Resin glycosides or caffeic acid contents were similar for the two genotypes in 1997, while higher level of resin glycosides was detected in Excel than in Beauregard in 1998. The interaction between drought stress and genotype was significant for adult feeding under free-choice conditions and for larval survival, indicating a different response between the two genotypes.