In mechanical deformation of crystalline materials, the critical resolved shear stress (CRSS; τ CRSS ) is the stress required to initiate movement of dislocations on a specific plane. In plastically anisotropic materials, such as Mg, τ CRSS for different slip systems differs greatly, leading to relatively poor ductility and formability. However, τ CRSS for all slip systems increases as the physical dimension of the sample decreases to approach eventually the ideal shear stresses of a material, which are much less anisotropic. Therefore, as the size of a sample gets smaller, the yield stress increases and τ CRSS anisotropy decreases. Here, we use in situ transmission electron microscopy mechanical testing and atomistic simulations to demonstrate that τ CRSS anisotropy can be significantly reduced in nanoscale Mg single crystals, where extremely high stresses (∼2 GPa) activate multiple deformation modes, resulting in a change from basal slip-dominated plasticity to a more homogeneous plasticity. Consequently, an abrupt and dramatic size-induced "brittleto-ductile" transition occurs around 100 nm. This nanoscale change in the CRSS anisotropy demonstrates the powerful effect of sizerelated deformation mechanisms and should be a general feature in plastically anisotropic materials.lightweight alloys | metallurgy | mechanical properties | in situ TEM | nanoparticle S trength and ductility are critical performance indicators of materials; in metals, both are associated with the activities of line defects in the crystalline lattice, called dislocation plasticity. Ductility is accomplished by the distributed and uniform multiplication and propagation of dislocations, whereas strengthening is often achieved by hindering their motion. Strength and ductility are fundamentally linked in materials, and a mechanism to improve one almost always leads to a decrease in the other (1, 2). How to achieve both high strength and high ductility is still a challenge of great importance in structural materials. Recent work has demonstrated that it is possible to improve both strength and ductility simultaneously, but this has mostly been limited to systems with ultrafine microstructures, such as nanotwinned Cu or twinning-induced plasticity steels (3, 4).As the lightest structural metal, Mg suffers from limited room temperature ductility and formability due to the highly anisotropic critical resolved shear stress (CRSS; τ CRSS ) of the different slip systems (5). In Mg, which has a hexagonal close-packed structure, the τ CRSS for nonbasal (prismatic and/or pyramidal) slip is ∼10 2 τ CRSS for basal slip (6, 7). Such an extreme plastic anisotropy of A ≡ τ nonbasal CRSS =τ basal CRSS ∼ 10 2 makes nonbasal slip very difficult to trigger. Without nonbasal slip or twinning (8), basal slip alone cannot accommodate arbitrary shape changes, and excessive basal slip in combination with unrelaxed tensile stresses in the plane-normal direction leads to spatially localized damage and rapid failure. Thus, a materials design strategy could be to enhanc...