Nickel-based single crystal (SX) turbine blades typically experience varying load conditions during operation. It is essential to consider the effects of changing stress and temperature when evaluating creep damage. The commonly used time-fraction method, based on the linear damage rule (LDR), has been demonstrated to be inconsistent with experimental results under certain loading conditions. There is a lack of research on damage accumulation under variable loading conditions specifically for SX superalloy. This paper conducted two-stage creep experiments for SX superalloy DD6 at 980 °C with stress levels of 230 MPa and 320 MPa, and at 1050 °C with stress levels of 135 MPa and 230 MPa. The load for the experiment was set based on the typical operating conditions of the SX turbine blades. The evolution of the microstructure under variable loading was observed using scanning electron microscope (SEM) and transmission electron microscope (TEM). The result of creep experiments revealed that the damage accumulation behavior of the SX superalloy does not conform to the LDR. Furthermore, in two-stage loading tests, the creep damage accumulation behavior differs from the classical sequence effect of fatigue loading. SEM and TEM analyses suggested that this phenomenon might be associated with the varying degradation rates of microstructures in SX superalloy.