We report on the magnetic and structural characterization of high lattice-mismatched [Dy 2nm /Sc t Sc ] superlattices, with variable Sc thickness t Sc = 2-6 nm. We find that the characteristic in-plane effective hexagonal magnetic anisotropy K 6,ef 6 reverses sign and undergoes a dramatic reduction, attaining values of ≈13-24 kJm −3 , when compared to K 6 6 = −0.76 MJm −3 in bulk Dy. As a result, the basal plane magnetic anisotropy is dominated by a uniaxial magnetic anisotropy (UMA) unfound in bulk Dy, which amounts to ≈175-142 kJm −3 . We attribute the large downsizing in K 6,ef 6 to the compression epitaxial strain, which generates a competing sixfold magnetoelastic (MEL) contribution to the magnetocrystalline (strain-free) magnetic anisotropy. Our study proves that the in-plane UMA is caused by the coupling between a giant symmetry-breaking MEL constant M 2 γ,2 ≈ 1 GPa and a morphic orthorhombiclike strain ε γ,1 ≈ 10 −4 , whose origin resides on the arising of an in-plane anisotropic strain relaxation process of the pseudoepitaxial registry between the nonmagnetic bottom layers in the superstructure. This investigation shows a broader perspective on the crucial role played by epitaxial strains at engineering the magnetic anisotropy in multilayers.