Using density-functional theory within the generalized gradient approximation, we investigate the energetics of oxygen subsurface adsorption governing the onset of bulk oxidation of Cu(100) surface. It shows that the presence of boundaries formed from merged missing-row nanodomains mismatched by a half unit-cell leads to preferred oxygen adsorption at the subsurface tetrahedral sites. The resulting Cu-O tetrahedrons along the domain boundary strikingly resemble that of the bulk oxide phase of Cu(2)O. These results provide direct atomic-scale insight into the microscopic origin of the crystallographic orientation relationships for oxide overlayer growth. Our results also suggest that the oxidation of an atomically flat terrace can still be a heterogeneous nucleation process controlled by defects in the oxygen-chemisorbed adlayer.