The tension-tension test with stress ratio 0.1 was conducted to clarify highcycle and very-high-cycle fatigue properties of Ni-based superalloy at 750 C by combining two-and three-dimensional microscopic observations. Results show that as stress level decreases, fatigue failure is less likely to be induced by pore, while the possibility of crystallographic facet-induced failure increases, and finally, the duplex S-N curves are formed. The larger roughness of crack nucleation region is mainly attributed to the geometric incompatibility of grains and the plastic deformation at crack tip. Under the influence of elevated temperature and vacuum environment, the transition size from small crack to long crack is approximately equal to the grain size. Combined with the evaluation of threshold values, the internal failure mechanism is elucidated. Finally, from the viewpoint of energy, a fatigue life prediction model is proposed, and the predicted results are in good agreement with the experimental ones.