Asphalt pavements experience damage due to traffic loading under various environmental conditions. Damage is caused by viscoplastic flow and microcracks, fracture due to fatigue, or fracture due to thermal effects. Asphalt pavements have the capability to recover from some of this damage depending on binder surface and rheological properties, filler surface properties, and length of rest periods. Asphalt mastic (asphalt and mineral filler) properties play a major role in controlling damage and healing. This paper addresses the development of a comprehensive methodology for the characterization of damage and healing in asphalt mastics. The methodology relies on nondestructive imaging techniques (X-ray CT), principles of continuum damage mechanics, and principles of micromechanics. The X-ray CT yields a damage parameter that quantifies the percentage of voids (cracks and air voids) in a specimen. The continuum damage model parameters are derived from the relationship between applied stress and pseudo strain. The micromechanics model relates the damaged mastic modulus to a reference undamaged modulus. This relationship is a function of internal structure properties (void size, film thickness, and percentage of voids), binder modulus, aggregate modulus, and bond energies within the mix. The internal structure properties are all obtained using X-ray CT. The developed methodology is employed to characterize damage in asphalt mastic based on experimental measurements using the Dynamic Mechanical Analyzer (DMA). Damage is monitored as a function of loading cycles, rest period, and moisture state (dry and wet conditions). The damage parameter measured by X-ray CT correlated very well with the predictions of the continuum and micromechanics models. All damage parameters were able to reflect the accumulation of damage under cyclic loading and were also able to capture the influence of moisture conditioning on damage. The healing due to rest periods was captured using X-ray CT, and it was reflected in the continuum and micromechanics damage models. Although this paper focused on fatigue cracking and healing at room temperatures, the methodology developed can be used to assess damage due to different mechanisms such as permanent deformation and low temperature cracking.