The microstructure, hardness, elastic modulus, and indentation creep of Ag/Cu multilayers prepared by magnetron sputtering were investigated by x-ray diffraction, transmission electron microscopy, and nanoindentation. The hardness values obey the Hall–Petch relationship as the periodicity decreases to 20 nm. For multilayers with periodicity smaller than 20 nm, the Hall–Petch relationship breaks down and the hardness values saturate at about 4.6 GPa; moreover, there are shear bands formed around their indents and strain bursts occurring during the load-holding process of indentation creep. These results imply that there is a transition of the deformation mechanism in the region where the periodicity is equal to 20 nm. This transition of the deformation mechanism can be ascribed to grain-size-dependent competition between the dislocations-mediated plasticity and grain-boundary sliding-mediated plasticity.