Age dependence on the hemispheric asymmetry alteration remains inconclusive partially due to the diversity of methodology. In this study, a multivariate model was applied to evaluate the evolution of the structural hemispheric asymmetry during healthy aging based on magnetic resonance imaging data. The T1-weighted images from 205 subjects were retrieved and categorized into 7 age groups. The morphological features including the surface area, mean curvature index, cortical thickness, and subjacent white matter volume in 34 regions of interest were calculated. The multivariate analysis was then performed on each age group to investigate the composite effect of the four features on asymmetry alterations. The P values were finally mapped onto a FreeSurfer template for visualization. Global reduction of hemispheric laterality was identified with a worse decline in parietal and occipital lobes as age advances. Reservation and left-right shift of laterality were vastly detected in the high-level cognition-related regions, which may imply a compensatory mechanism of healthy brain counteracting the age-associated functional impairment. The age dependence on the hemispheric asymmetry may embed mechanisms that underlie the behavioral and cognitive declination associated with age related neuropsychological diseases.