The unique crystallographic lamellar microstructure (CLM) Ni-based superalloys fabricated by laser powder bed fusion (LPBF) exhibits excellent tensile properties. This study aims to investigate CLM’s high-temperature stress rupture behavior and use these findings to improve the additive manufacturing process. The result shows that the high temperature-induced intergranular fracture in <110> grain region is responsible for stress rupture failure under both conditions of 760 °C/780 MPa and 980 °C/260 MPa. Among them, the sub-grain boundary fracture occurs only under high temperature and low stress, 980 °C/260 MPa. Due to the severe intergranular fracture induced by stray grains, the stress rupture life is very low under both conditions. According to the finite element simulation, the formation of stray grains stems from the unstable heat flow within the melt pool during the process. In addition, the shorter stress rupture lifetime does not excite a more pronounced dislocation network around the γ′ phase. However, the deformation twins can still be activated inside the <110> grains, so it has excellent plasticity under both test conditions. Finally, this work indicates that the future optimization of CLM by LPBF should focus on eliminating of high-angle grain boundaries in <110> grains.