High-power laser melting deposition provides an efficient solution for the fabrication of large-sized titanium alloy components. In this study, Ti6Al4V blocks with well-formed structures were prepared using a 7 kW laser power, and their internal defect distribution, microstructure along the deposition direction, tensile properties, and fatigue performance were investigated. The results showed that the density of the as-deposited Ti6Al4V blocks could reach 99.94%, and the main internal defects were cavities, primarily spherical and dispersed, with a maximum diameter of 326.7 μm. Among them, 65.53% of cavities had a diameter smaller than 100 μm, and 92.76% had a diameter smaller than 200 μm. The microstructure at the top region of the specimen consisted of a needle-shaped α phase, the middle region had a mixture of needle-shaped and lamellar α-phase, and the bottom region showed a lamellar α-phase structure. With an increase in deposition height, the aspect ratio of α-phase increased, and the average width decreased from 3.22 μm to 0.88 μm. The internal structure was mainly composed of a basket-weave structure, with a small amount of Widmanstätten structure present at grain boundaries. Hardness and tensile properties exhibited significant non-uniformity along the deposition height. The tensile strength and yield strength at the top region were approximately 50 MPa higher than those in the middle and bottom regions, while the elongation was about 2% lower. The top region's tensile fracture surface displayed a sawtooth pattern, whereas the middle and bottom regions exhibited fractures along the 45° direction of the principal stress. The length of α-bundles and the interface density within the bundles were crucial factors affecting crack propagation. In the top region, α bundles were the longest, and the interface density was the highest. During crack propagation, when the crack extended perpendicular to the α bundles, it encountered high resistance, and when it extended non-perpendicular, it rapidly propagated along the bundle boundaries, exhibiting high strength and low plasticity. The fatigue performance of the Ti6Al4V specimens fabricated by high-power laser melting deposition showed significant dispersion, with cracks originating from subsurface lack of fusion defects. At different stages of fatigue crack propagation, the role of α phase laths varied: during the fatigue source region, cracks primarily propagated along the boundaries of α laths, displaying significant cleavage fracture characteristics. In the fatigue propagation region, crack propagation velocity was mainly influenced by the direction of the laths, and in the fatigue final rupture region, ductile fracture was predominant. Α laths parallel to the tensile direction exhibited the best plasticity, promoting the formation of large dimples and high tear ridges.