Abstract: The high-efficiency welding of large-sized thick near β titanium alloy components is highly required in engineering fields. However, their main welding methods currently encounter either low welding efficiency (arc welding) or too high vacuum condition (electron beam welding). Furthermore, there is a common problem with a significant joint strength reduction after welding because of few precipitations of the strengthening α phase, largely hindering their application. In this study, the full penetration of 50-mm-thick near β titanium alloy Ti-5Al-5Mo-5V-3Cr-1Zr was achieved for the first time via vacuum laser beam welding (VLBW). After VLBW, the double annealing treatment was designed to regulate the microstructure to enhance the joint strength. Among various annealing treatments (high-temperature annealing at 750-870℃ + low-temperature annealing at 600℃), the 830℃ + 600℃ double heat-treatment process enhanced the joint strength most, with the increase in the yield and tensile strengths from 804.9 MPa and 814.6 MPa for the as-welded joint to 1340.4 MPa and 1358.6 MPa for the annealed joint, reaching more than 98% of the BM. The great strength increase was mainly attributed to the formation of the multi-level lamellar microstructure with 10.15vol% of primary α (αp) + 42.57vol% of secondary α (αs). This structure was achieved via the nucleation and growth of αp phase within the metastable β phase during high-temperature annealing and the precipitation of αs phase from β grains during low-temperature annealing. It mainly enhanced the joint strength by strengthening the β matrix and increasing the αp/β and αs/β interfaces. Among these, the αs phase played a more dominant role in strengthening compared to the αp, as the joint strength increased significantly with the rise in the αs volume fraction. This study provides a VLBW + annealing treatment method to achieve high strength joints of near β titanium alloy thick plates.