Damage to building structures due to underground blast-induced ground motions is a primary concern in the corresponding determination of the safe inhabited building distance (IBD). Because of the high-frequency nature of this category of ground motions and especially the presence of significant vertical component, the characteristics of structural response and damage differ from those under seismic type low-frequency ground motions. This paper presents a numerical investigation aimed at evaluating reinforced concrete (RC) structure damage generated by underground blast-induced ground excitation. In the numerical model, two damage indices are proposed to model reinforced concrete failure. A fracture indicator is defined to track the cracking status of concrete from micro- to macrolevel; the development of a plastic hinge due to reinforcement yielding is monitored by a plastic indicator; while the global damage of the entire structure is correlated to structural stiffness degradation represented by its natural frequency reduction. The proposed damage indices are calibrated by a shaking table test on a 1: 5-scale frame model. They are then applied to analyse the structural damage to typical low- to high-rise RC frames under blast-induced ground motions. Results demonstrate a distinctive pattern of structural damage and it is shown that the conventional damage assessment methods adopted in seismic analysis are not applicable here. It is also found that the existing code regulation on allowable peak particle velocity of blast-induced ground motions concerning major structural damage is very conservative for modern RC structures.