By functionalizing the surfaces of ZnO nanobelts (NBs) with a thin self-assembled molecular layer, the electrical and optoelectronic performances of a single NB-based device are drastically improved. For a single NB-based device, due to energy band tuning and surface modification, the conductance was enhanced by 6 orders of magnitude upon functionalization; a coating molecule layer has changed a Schottky contact into an Ohmic contact without sophisticated deposition of multilayered metals. A functionalized NB showed negative differential resistance and exhibited huge improved photoconductivity and gas sensing response. The functionalized molecular layer also greatly reduced the etching rate of the ZnO NBs by buffer solution, largely extending their life time for biomedical applications. Our study demonstrates a new approach for improving the physical properties of oxide NBs and nanowires for device applications.