Through creep performance tests, microstructural observations, and contrast analysis of the dislocation configuration, the deformation and damage mechanism of the directionally solidified nickel-based superalloy during creep at moderate temperatures was investigated. The findings suggested that the deformation of the alloy in the late stage of creep at moderate temperatures involved dislocations slipping in the γ matrix and shearing into the γ′ phase. The super-dislocations sheared into the γ′ phase could either be decomposed to form a <112> super-Shockley incomplete dislocation plus superlattice intrinsic stacking fault (SISF) configuration, or it could slip from the {111} plane to the {100} plane and decompose to form a dislocation configuration of the Kear–Wilsdorf (K-W) lock plus antiphase domain boundary (APB). The configurations of the dislocations could inhibit the slipping and cross-slipping of dislocations to enhance the alloy creep strength, which is thought to be one reason that the alloy displayed good creep resistance. In the late creep stage, the primary/secondary slipping systems were alternately activated, and the interaction of the slipping traces caused micro-holes to appear on the interface of the γ/γ′ phases at the intersection areas of the two slipping systems. The micro-holes gathered and grew to form micro-cracks, which extended along the grain boundary at 45° to the stress axis until creep rupture occurred. These were the damage and fracture characteristics of the alloy in the late stage of creep at moderate temperatures.