A significant challenge in improving metal-based wire-arc directed energy deposition (WDED) for additive manufacturing is the lack of knowledge about microstructure evolution and its correlation with layer-wise plastic response and bulk tensile behavior. For the first time, this paper establishes the role of crystalline orientation, dislocation densities, and layer-by-layer strength on the anisotropy of bulk uniaxial tensile deformation in commercially pure titanium (cp-Ti) processed by WDED. An integrated approach that combines microscopy, spectroscopy, millimeter-scale indentation and centimeter-scale uniaxial tensile techniques is adopted. The variation in thermal cycles during WDED results in a higher grain orientation spread greater than 5° in the longitudinal direction (LD) parallel to arc motion compared to about 4° along the normal direction (ND) of additive buildup. Similarly, the statistically stored dislocation density in LD, 1.8 x 1016 m−2, is double that in ND, 0.9 x 1016 m−2. These factors result in a greater strain localization in the LD than in ND. The higher strain localization results in plastic anisotropy manifested as material buildup and ductility, which are 40 μm and 33 % higher in ND than in LD. On the other hand, the monolithic macrostructure and absence of weak points at layer interfaces of the cp-Ti component led to comparable yield and ultimate tensile strengths across the individual layers and the bulk component at 311–328 MPa and 369–385 MPa, respectively. These properties are about 90 % of those in conventionally cast commercially cast titanium. Thus, the comprehensive understanding of titanium's nuanced isotropic strength and anisotropic ductility constitutes a major step in advancing WDED as a large-scale additive manufacturing technology and establishing a standardized database of mechanical properties.