In this study, we demonstrated for the first time the growth of ZnO nanowires (NWs) decorated with highly crystalline few-layer PbI2 and fabricated two-terminal single-nanowire photodetector devices to investigate the photoelectric properties of the hybrid nanostructures. We developed a novel two-step growth process for uniform crystalline PbI2 nanosheets via reactive magnetron deposition of a lead oxide film followed by subsequent iodination to PbI2 on a ZnO NW substrate, and we compared as-grown hybrid nanostructures with ones prepared via thermal evaporation method. ZnO–PbI2 NWs were characterized by scanning and transmission electron microscopy, X-ray diffraction analysis and photoluminescence measurements. By fabricating two-terminal single-nanowire photodetectors of the as-grown ZnO–PbI2 nanostructures, we showed that they exhibit reduced dark current and decreased photoresponse time in comparison to pure ZnO NWs and have responsivity up to 0.6 A/W. Ab initio calculations of the electronic structure of both PbI2 nanosheets and ZnO NWs have been performed, and show potential for photoelectrocatalytic hydrogen production. The obtained results show the benefits of combining layered van der Waals materials with semiconducting NWs to create novel nanostructures with enhanced properties for applications in optoelectronics or X-ray detectors.