Bulk ZnO has traditionally been regarded as multifunctional materials for energy and optoelectronics applications. Recently, exploring this material at the nanoscale has been reported and seeking a proper substrate is highly desired. In this work, the structural and electronic properties of graphene like ZnO two-dimensional (2D) monolayer are investigated by first principles calculation based on density functional theory. The alignment of the valence and conduction bands of ZnO with the state of Cu substrate is analyzed. Particularly the attention has been focused on the establishment of a Schottky contact and interfacial charge transfer between the 2D ZnO monolayer and Cu substrate. It is predicted that the electronic charges are accumulated on the Zn and O atoms due to d–d hybridization between Cu and Zn . Our study reveals that the significant interaction between the ZnO and Cu can greatly modify the electronic properties of the ZnO and suggests potential applications in nanoelectronic devices.