In this study, a dual-scale numerical procedure is developed to reveal the creep-fatigue damage mechanisms and estimate the crack initiation life for notched structures made of Inconel 718 superalloy at 650 °C. The macro-scale simulation solves the creep-fatigue deformation behavior with viscoplastic constitutive models, and the local deformation histories are supplied to the micro-scale simulation as boundary conditions. In the micro-scale simulation, the local damage evolutions are solved based on crystal plasticity combined with grain boundary cavity model. The creep damage is calculated by a special formulation in the form of cavity nucleation, growth and coalescence. The fatigue damage is represented by accumulated energy dissipation originated from crystal plasticity finite element simulation. Experimentally, the creep-fatigue tests of notched structures are carried out for Inconel 718 superalloy at 650 °C to validate the feasibility and robustness of the proposed numerical procedure. Moreover, the crack initiation behavior, including transgranular cracks under fatigue loading and intergranular cracks under creep-fatigue loading, is explained through different types of microstructure observations together with a dual-scale numerical procedure. In detail, the crack initiation sites transferred from the grain interior at notched surface to the grain boundaries at notched subsurface with an increase in hold times can be well predicted by the proposed numerical procedure. In addition, the simulated life based on the developed life prediction approach agrees well with the experimental data within an error band of ±2. Parametric studies show that the creep damage is more sensitive to grain boundary diffusion than to the external conditions of strain level and hold time.