To investigate the anisotropic behavior of Ti–6Al–4V alloys generated by Laser Engineering Net Shaping (LENS), a simulation process based on cellular automaton and crystal plasticity finite elements was established. The accuracy of the microstructural simulation based on Cellular Automaton was validated by Electron Backscatter Diffraction technology. Crystal orientation parameters were extracted from cellular automaton model simulations and a representative volume element (RVE) was constructed. Based on the experimentally observed α + β dual-phase microstructure, the α + β morphology was generated in the RVE (Representative Volume Element) using the Burgers Orientation Relationship. The mechanical behavior and properties of RVE were predicted using the crystal plasticity finite element model, and the accuracy of the simulation process was verified through experiments. RVE with different α phase volume fractions and equiaxed grains were established for crystal plasticity finite element simulations. The results indicate that the Ti–6Al–4V alloy produced by LENS exhibits anisotropic behavior and properties. Higher tensile strength and elastic modulus are demonstrated by the alloy at a 45°direction. The tensile strength of the sample along the build direction is the lowest, yet exhibits the highest ductility. The alloy's plasticity is reduced when subjected to loading perpendicular to the direction of the columnar grains. Additionally, stress concentration along the grain boundaries is increased, leading to easier nucleation and propagation of cracks near these boundaries. A linear increase in tensile strength with α phase volume fraction is demonstrated.