In order to investigate the anisotropic micromechanical properties of single-crystal nickel-based superalloy DD99 of four crystallographic orientations, (001), (215), (405), and (605), microindentation test (MIT) was conducted with different loads and loading velocities by a sharp Berkovich indenter. Some material parameters reflecting the micromechanical behavior of DD99, such as microhardnessH, Young’s modulusE, yield stressσy, strain hardening componentn, and tensile strengthσb, can be obtained from load-displacement relations.HandEof four different crystal planes evidently decrease with the increase ofh. The reduction ofHis due to dislocation hardening whileEis related to interplanar spacing and crystal variable.σyof (215) is the largest among four crystal planes, followed by (605), and (001) has the lowest value.nof (215) is the lowest, followed by (605), and that of (001) is the largest. Subsequently, a simplified elastic-plastic material model was employed for 3D microindentation simulation of DD99 with various crystal orientations. The simulation results agreed well with experimental, which confirmed the accuracy of the simplified material model.