<p>TC11 titanium alloy is favored in reusable launch vehicles due to its excellent high-temperature performance, though achieving high toughness remains a challenge. Wire arc additive manufacturing (WAAM) offers a promising approach, yet its distinct microstructures differ considerably from those of traditionally manufactured TC11 alloys, rendering existing fracture toughness data and prediction models inadequate. This study evaluates WAAMed TC11 samples subjected to various heat treatments to explore the impact of microstructure on fracture toughness. A novel prediction model is developed, considering both intrinsic and extrinsic factors influencing toughness. Results indicate that horizontal 550-AC (550 ℃/4&#xa0;h/air cooling) samples exhibit the lowest fracture toughness of 76.3&#xa0;MPa·m^1/2, with an anisotropic difference of up to 18.5&#xa0;MPa·m^1/2 compared to vertical samples. This is attributed to continuous α phase (<i>α</i>_P) grain boundaries and a basket-weave microstructure, which fail to effectively deflect cracks. Conversely, 970-AA (970 ℃/2&#xa0;h/air cooling + 550 ℃/4&#xa0;h/air cooling) and 990-AA (990 ℃/2&#xa0;h/air cooling + 550 ℃/4&#xa0;h/air cooling) samples demonstrate significant improvements in fracture toughness, with the 990-AA sample achieving the highest values of 113&#xa0;MPa·m^1/2 and 115.2&#xa0;MPa·m^1/2 in horizontal and vertical directions, respectively. The crab-like <i>α</i>_P and secondary <i>α</i>_s enhance crack growth tortuosity and fracture surface roughness, improving fracture resistance and reducing anisotropy. Furthermore, fracture toughness is governed by both intrinsic and extrinsic factors, with intrinsic toughness dominating (69–81% of total toughness). The proposed model maintains a prediction error within 15%, offering a reliable tool for assessing fracture toughness in WAAMed TC11 alloys.</p>