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We compare the indentation hardness of crystal/crystal (C/C) Cu/Zr multilayers and the crystal/amorphous (C/A) Cu/Cu–Zr multilayers with equal individual layer thicknesses spanning from 1 to 200nm. Both systems show similar layer thickness dependent evolution of hardness. At smaller layer thickness the C/C multilayers show softening, while no softening is observed in the C/A multilayers. The layer thickness dependent hardness is quantitatively estimated by using dislocation models. The significance of crystalline (Zr) layer and amorphous (Cu–Zr) layer on plastic deformation mechanisms is discussed.