Abstract: An optimization study on the process parameters of vacuum laser welding for Ta10W alloy lap joints was conducted, and the influence law of different process parameters on the weld formation was systematically analyzed. The microstructural features and mechanical properties of the Ta10W alloy weld were characterized, and the correlation between the microstructure and macroscopic performance was established. Experimental results demonstrate that when the ambient pressure is 20 Pa, the oxidation phenomenon of the welded joint can be significantly suppressed, and the weld surface formation quality is significantly improved. For the lap joint, a partial penetration weld format is required, and a combination of high-power and high-speed welding parameters is optimal. In this paper, for the specimen with a thickness of 1.5 mm, the optimal welding process parameters obtained under the vacuum environment are as follows: laser power of 5 kW, welding speed of 2.5 m/min, and defocus amount of + 3 mm. The microstructure of the T-shaped lap weld mainly consists of columnar crystals and equiaxed crystals; the columnar crystals are predominantly distributed in the upper region of the weld, and more equiaxed crystals exist in the central bottom region of the weld. Under the optimal process parameter conditions, the bonding interface width of the Ta10W alloy laser-welded lap joint is 1.29 mm; the joint shear strength reaches 389 MPa; all the specimen fractures occur in the weld zone.