Dissimilar metal welds are commonly used in nuclear power plants to connect low alloy steel components and austenitic stainless steel piping systems. The integrity assessment and life estimation for such welded structures require consideration of residual stresses induced by manufacturing processes. Because the fabrication process of dissimilar metal weld joints is considerably complex, it is very difficult to accurately predict residual stresses. In this study, both numerical simulation technology and experimental method were used to investigate welding residual stress distribution in a dissimilar metal pipe joint with a medium diameter, which were performed by a multi-pass welding process. Firstly, an experimental mock-up was fabricated to measure the residual stress distributions on the inside and the outside surfaces. Then, a time-effective 3-D finite element model was developed to simulate welding residual stresses through using a simplified moving heat source. The simplified heat source method could complete the thermo-mechanical analysis in an acceptable time, and the simulation results generally matched the measured data near the weld zone. Through comparing the simulation results and the experimental measurements, we can infer that besides the multi-pass welding process other key manufacturing processes such as cladding, buttering and heat treatment should also be taken into account to accurately predict residual stresses in the whole range of the dissimilar metal pipe.