The creep behavior and deformation mechanism of the nickel-based single-crystal superalloy containing 6wt% Re and 5wt% Ru at ultra-high temperatures were studied via microstructure observation and creep property analysis. The results show that under the condition of 1160 °C/120 MPa, the Ni-based superalloy has a creep life of 206 h. During the steady state creep period, the deformation mechanism is dominated by dislocation glide in the γ matrix and dislocation climb over the γ′ raft phases. The refractory elements dissolved in the γ matrix can improve the resistance to dislocation movement. In the late creep stage, the cross-slip occurs from {111} plane to the {100} plane with the dislocations used for shearing the γ′ phase, and then the Kear-Wilsdorf (K-W) dislocation locks are formed. A large number of K-W dislocation locks can inhibit the dislocation glide and cross-slip, thus improving the creep resistance and reducing the strain rate for Ni-based superalloys. In the late creep stage, the cross-slip dislocations are initiated to twist the γ′/γ raft phases, and the crack initiation and propagation occur in the γ′/γ interfaces until fracture. These phenomena are the damage and fracture features of the Ni-based superalloys. The Ru atoms dissolved in the γ′ phase can replace the Al atoms. When Ru, Re, and W atoms react in the Ni-based superalloy, more Re and W atoms can be dissolved into the γ′ phase, which reduces the element diffusion rate and hinders the dislocation movement, thereby retaining more K-W dislocation locks and excellent creep resistance of Ni-based superalloys at ultra-high temperatures.