The anisotropic of microstructure for additively manufactured Al alloys is attributed to sharp temperature gradient during laser melting, resulting in anisotropy of mechanical properties. The correlation of grain orientation, size and aspect ratio on mechanical properties were investigated using in-situ EBSD tensile method on selective laser melting Al–Mn-Sc alloys in longitudinal section and cross section. The lattice rotation behavior and the effects of grain orientation, grain size and aspect ratio on mechanical anisotropy were explored. The predominant <001> orientation of the columnar crystals in the longitudinal section and the <102 > and <101> orientation that dominates the equiaxed crystals in the cross-section had a certain influence on the anisotropy of mechanical properties. The grains with different shapes and sizes exhibited different rotation behavior, and lattice rotation of equiaxed crystals with smaller grain sizes was more complex. By introducing anisotropy coefficients (Ka), the anisotropy sensitivity to grain orientations was revealed. Based on the anisotropy coefficient, grain size and aspect ratio, the mechanical anisotropy in both directions was accurately predicted.