The present study aimed to experimentally evaluate the mechanical properties of Pb(In1/2Nb1/2)O3–Pb(Mg1/3Nb2/3)O3–PbTiO3 (PIN–PMN–PT) bulk single crystals with different crystallographic directions using the nanoindentation technique. The load–indentation depth curves, elastic and plastic deformations, hardnesses, and Young’s moduli of [100]- and [110]-oriented 0.28PIN–0.43PMN–0.29PT bulk single crystals were investigated. Our results show that with an increase in the maximum indentation depth hmax, the plastic residual percentage increased for both the [100]- and the [110]-oriented single crystals. At each hmax, the plastic residual percentage of the [100]-oriented PIN–PMN–PT single crystals was less than that of the [110]-oriented PIN–PMN–PT single crystals. At hmax from 500 nm to 2000 nm, the plastic deformation was larger than the elastic deformation, and the plastic residual percentage was larger than 50% for both the [100]- and the [110]-oriented single crystals. This means that the plastic deformation dominated in the indentation process of PIN–PMN–PT single crystals. The indentation size effect on the hardness of the PIN–PMN–PT single crystals was apparent in the nanoindentation process. Both the hardness and the Young’s modulus of the [100]-PIN–PMN–PT single crystals were greater than those of the [110]-PIN–PMN–PT single crystals, which indicates that the PIN–PMN–PT single crystals had anisotropic mechanical characteristics.