The microstructure of asphalt affects the micro-mechanical properties. In this study, atomic force microscopy (AFM) was used to investigate the surface elastic modulus and nanohardness of asphalt binder. Relevant mechanical indexes were quantitatively evaluated by contact mechanical model. Five types of asphalts, including different grades, oil sources, and before and after modification, were selected as test objects, and the effects of asphalt binder type, aging, water, and anti-stripping agent on the asphalt micromechanics were explored. The results showed that the micromechanical properties of asphalt binder are affected by grade, oil source, and modification. The aging resistance of modified asphalt binder is better than that of unmodified asphalt binder. Water immersion reduces the surface micromechanical properties of the asphalt binder. The effect of the anti-stripping agent on the modified asphalt binder is greater than that of the unmodified asphalt binder.