Abstract: In order to realize high effective preparation of large-sized metal sandwich structure, the laser penetration overlay welding process of 921A steel T-joint was studied by response surface method and central composite design test, and the calculation model of weld width and joint tensile strength was established. On this basis, the welding process was optimized and verified. The results show that the most significant factors affecting the weld width are welding speed, defocus amount and welding speed × defocus amount, and the maximum error between the predicted value of the model and the actual value of the test is less than 5%. For the tensile strength of the joint, the most significant factors are welding speed and welding speed × defocusing amount, and the maximum error between the predicted value of the model and the actual value of the test is less than 10%. The optimum process parameters are laser power of 4750 W, welding speed of 0.48 m/min and defocusing amount of 4 mm. Under the process, the sample breaks at the base metal, indicating that the tensile strength of the joint is better than that of the base metal.