Hybrid ZnO@Ag core-shell nanorods have been synthesized by a synthetic strategy based on seed mediated growth. Formation of core-shell nanostructures was confirmed by UV- diffused reflectance spectroscopy (UV-DRS), X-ray diffraction studies, field emission scanning electron microscopy and high resolution transmission electron microscopy. UV-DRS analysis of hybrid core-shell nanorods suggests the possibility of interfacial electron transfer between surface anchored Ag nanoclusters and ZnO nanorods. Successful decoration of Ag nanoclusters with an average diameter of ~7 ± 0.5 nm was observed forming the heterojunctions on the surface of the ZnO nanorods. An enhanced antibacterial property was observed for the ZnO@Ag core-shell nanorods against both Staphylococcus aureus and Pseudomonas aeruginosa lbacteria. The synergetic antibacterial activity of ZnO@Ag nanorods was found to be more prominent against Gram-positive bacteria than Gram-negative bacteria. The plausible reason for this enhanced antibacterial activity of the core-shell nanorods can be attributed to the physical damage caused by the interaction of the material with outer cell wall layer due to the production of reactive oxygen species by interfacial electron transfer between ZnO nanorods and plasmonic Ag nanoclusters. Overall, the ZnO@Ag core-shell nanorods were found to be promising materials that could be developed further as an effective antibacterial agent against wide range of microorganisms to control spreading and persistence of bacterial infections.