The distribution law of residual stress in multi-channel scanned plasma cladding of Co-based alloy under different process parameters was studied by means of simulation and tests, and the optimum process parameters were optimized. The simulation model of the plasma cladding stress field was established by ABAQUS software, and the influence law of the working current, scanning speed, and scanning mode on the residual stress of the Co-based alloy multi-channel scanning was studied. A set of optimal cladding process parameters were obtained. The residual stress of the cladding layer was measured by the blind hole method and compared with the stress value in the finite element model. The results show that there is residual tensile stress on the surface of the cladding layer. The residual stress along the direction of the scanning path is greater than that along the direction of the scan sequence. The residual stress increases with the increase of the working current. The scanning speed is greater, and the residual stress is smaller. The residual stress of the short-edge scanning is greater than that of the long-edge scanning. The residual stress of the successive scanning is greater than that of the reciprocating scanning. The long-edge reciprocating scanning is the best scanning mode. The best combination of process parameters is the working current of 90 A, the scanning speed of 100 mm/min, and the long-edge reciprocating scanning mode.