Welding is the key manufacturing method for nuclear reactors and components. For nuclear reactors and components, ferritic heat resistant steels and nickel-based filler metals are the popular material selections. However, due to the different mechanical properties of iron-based and nickel-based materials, the weld angle and the form of macro-interface between them affect the stress and strain distributions in dissimilar metal welded structures and thus affect the service life of nuclear reactors and components. Here, we selected different Fe/Ni interface forms to investigate the effects on service life of dissimilar metal welded structures, namely I-type Fe/Ni interface, Y-type Fe/Ni interface and step-type Fe/Ni interface. The relationship between failure location and service life was clarified by means of finite element framework and creep tests. We analyzed and discussed the evolutions of stress and strain in dissimilar metal welded structures to determine the contribution of mechanical factors to failure. Meanwhile, the microstructures in the ruptured dissimilar metal welded structures were observed to understand micro-mechanism of failure. Creep life of the welded structure with Y-type Fe/Ni interface was longer than that with I-type Fe/Ni interface. The failure location of the welded structure with I-type Fe/Ni interface was along Fe/Ni interface, while the failure location of the welded structure with Y-type Fe/Ni interface and step-type Fe/Ni interface were in iron-based heat-affected zone and base metal. The failure of welded structure with I-type Fe/Ni interface was due to microstructure degradation, stress/strain concentration and oxide notch. The failure of welded structure with Y-type Fe/Ni interface was mainly related to Type IV fracture. The Y-type interface form could separate stress/strain concentration in welded structure from Fe/Ni interface and the step-type Fe/Ni interface could lead to crack propagation into ferritic steel, thus prolonging creep life. This work suggests that the Fe/Ni interface form in welded structure can be optimized by adjusting the welding angle, so as to make welding more advanced manufacturing method to improve the service reliability of nuclear components.