This study investigated whether the natural flavonoids myricetin and quercetin could enhance the susceptibility of Escherichia coli to bacteriophage infection by suppressing the activity and transcription of the molecular chaperone DnaK. The dnaK deletion mutant exhibited significantly greater susceptibility to phage S127BCL3 than the wild-type strain. Pretreatment with myricetin or quercetin increased phage-mediated killing in both E. coli BW25113 and E. coli O157:H7, while significantly reducing the transcription of the chaperone genes dnaK, dnaJ, groEL, and grpE. These findings demonstrate that flavonoid pretreatment enhances phage susceptibility by impairing bacterial stress-response systems and suggest that combining bacteriophages with flavonoids could provide a promising and safe biocontrol strategy against foodborne bacterial pathogens.