In this paper, we address the effect of shell thickness and core/shell structure on the electrochemical and photoelectrochemical cell (PEC) measurements properties of ZnO/In2S3 core/shell nanowires (NWs). The objective is to elucidate the mechanisms responsible for the extended photoresponse of ZnO/In2S3 core/shell NWs to solar radiation. Well aligned ZnO/In2S3 core/shell NWs were fabricated on indium tin oxide substrates using electrochemically grown ZnO NWs as the cores and electrodeposited In2S3 as the shells. The samples structure was characterized by X-ray diffraction, revealing the mixed wurtzite and tetragonal structures of both ZnO cores and In2S3 shells, and the improvement in the structure with the increases of In2S3 shell thickness. The optical properties were studied through optical absorbance and photoluminescence measurements, showing the optical properties featured with type-II heterogeneous nanostructures constructed from ZnO and In2S3. Electrochemical impedance spectroscopy (EIS) is employed and an equivalent circuit model is designed suggesting that the cell performances were affected by increasing In2S3 shell deposition times. From Mott–Schottky plots, several parameters such as flat-band potential and free carrier concentration were determined. Next, from (PEC) measurements, the highest photocurrent density produced by the In2S3 shell electrode prepared at deposition time of 5 min reached 9.30 mA cm2 at an applied potential of 0.8 V vs. Ag/AgCl. This value was about 6.8 times as much as more than that measured on ZnO NWs one and provided the highest value of solar-to-hydrogen energy efficiency η (%). These results are very encouraging and suggest that In2S3 covered ZnO NWs nanostructures are valuable photo-anodes in order to build cheap devices for solar energy-to-hydrogen generation devices.