ZnO has been extensively studied by virtue of its remarkably high piezoelectric responses, especially in nanowire forms. Currently, the high piezoelectricity of wurtzite ZnO is understood in terms of the covalent-bonding interaction between Zn 3d and O 2p orbitals. However, the Zn 3d orbitals are not capable of forming hybridized orbitals with the O 2p z orbitals since the Zn ion is characterized by fully filled non-interacting 3d orbitals. To resolve this puzzling problem, we have investigated the atomicscale origin of piezoelectricity by exploiting density-functional theory calculations. On the basis of the computed orbital-resolved density of states and the band structure over the G-M first Brillouin zone, we propose an intriguing bonding mechanism that accounts for the observed high piezoelectricityintra-atomic 3d z 2-4p z orbital self-mixing of Zn, followed by asymmetric hybridization between the Zn 3d z 2-4p z self-mixed orbital and the O 2p z orbital along the polar c-axis of the wurtzite ZnO.