Titanium alloys fabricated by wire and arc additive manufacturing (WAAM) are prone to produce defects with coarse intracrystalline α lamellae, continuous grain boundary of α phase (GB-α), and chemical segregation. The synergistic combination of the factors leads to high strength at the expense of plasticity. Adding activating flux of CaF2 during WAAM can provide an effective way to achieve a remarkable strength-ductility combination of Ti–6Al–4V alloy. Adding CaF2 produced refined intragranular α lamellae, discontinuous GB-α with dowel-like α lamellae (DL-α, primary α phase penetrated through the GB-α and embedded within adjacent β grains), as well as achieved concentration modulations. The tailored microstructure induced multistage strain hardening behavior (sequentially activated multiple strain hardening) during tensile plastic deformation, which allows WAAM-fabricated Ti–6Al–4V alloy a high tensile strength with good plasticity. The good strength-ductility balance is mainly attributed to the utilization of multiple strengthening mechanisms in titanium alloys. This study provides a novel method to improve the mechanical properties of WAAM-fabricated titanium alloys.