Based on different additive manufacturing building directions, four groups of Ti–6A1–4V primitivecubic (PC) lattice samples fabricated by selective laser melting (SLM) with various relative densities were investigated for the effects of the building directions on the mechanical properties of the lattice structures. The mechanical properties were obtained by numerical simulations and uniaxial compression tests, and the microscopic morphology of the samples defects was analyzed. The results show that the manufacturing defects caused by different building directions will change the effective Young's modulus in different directions and failure mode of the lattice structure. The specimens with low relative densities collapsed layer by layer randomly, and the high-density lattice structures collapsed by the diagonal shear failure. The lattice structure strut defects caused by SLM increased with the increase of the angle between building direction and the struts, and the defects lead a decrease in effective Young's modulus. The manufacturing defects of the low-density lattice structures were more sensitive to the building direction, and due to the internal defects of additive manufacturing, the simulation results based on the homogenization theory are higher than the experimental values.