The aim of this study is to investigate the change of mechanical properties of human dentin due to aging and spatial variation. Sections of coronal dentin are made from human molars in three groups: young, mid-aged, and old patients. A nanoindentation test is conducted from regions near the pulp to the dentin-enamel junction (DEJ) to evaluate the load-depth indentation response and determine Young’s modulus and hardness. Based on the loading and unloading load-displacement curves in nanoindentation, a numerical model of plastic damage is used to study the plastic and the damage behaviors and the contribution to the degradation in the unloading stiffness. The experimental results show that Young’s modulus of the inner dentin is significantly lower than that of outer dentin in each age group. Compared with the young dentin, the old dentin has greater hardness and Young’s modulus with similar spatial variations. The magnitudes of the yield strength and the damage variable are also affected by aging and vary with spatial locations. In the same age group, the yield strength in inner dentin is lower than those in middle and outer dentin, more damage occurs with similar spatial variations, and the yield strength of young dentin is generally lower and causes more damage compared with those in both the mid-aged and old groups.