Control of nucleation and growth of graphene during the chemical vapor deposition (CVD) synthesis is crucial for achieving large-area and high-quality graphene single-crystals.The metal steps and grain boundaries were still regarded as the main starting points of graphene CVD growth on transition-metal surfaces.Here we discovered that the microdefects of metal copper surface played more important role in the nucleation and growth of graphene on the basis of comprehensive experimental and theoretical studies.The surface microdefects of Cu foil were first identified by the hydrogen etching experiment of graphene domains.On the basis of density functional calculations, the microdefects were found as the main nucleation centers due to the relative low nucleation barrier of graphene around the microdefects.The density of graphene nuclei can be reduced by decreasing the microdefects implemented by the polishing of Cu foil, which contributes to the formation of large-area graphene with low-density grain boundaries.