One of the challenges of additive manufacturing (AM) technology is the inability to generate repeatable microstructure and mechanical properties in different orientations. In this work, the effect of build orientation on the microstructure and mechanical properties of Ti–6Al–4V specimens manufactured by selective laser melting (SLM) was studied. The samples built in the Z orientation showed weaker tensile strength compared to the samples built in X, and Y orientations. Samples built in X and Y orientations exhibited brittle fracture features in areas close to the substrate and ductile fracture features in the area farther from the substrate. Defects including pores, cracks, and unmelted/partially-melted powder particles contributed to lower tensile and fracture toughness properties in different orientations.