In this paper, damage mechanisms, failure modes and progressive collapse mechanism of RC frame structures under blasting loading are studied and some parameters, such as explosion sites, distances and explosion equivalent are considered. Furthermore, nonlinear finite element (FE) dynamic analysis of the RC frame structures under blasting loads is conducted. Following conclusions can be drawn from the experiments and numerical simulation: (1) The damage under internal explosion is much greater than that caused by external explosion. Major damage emerged in the beams and columns under external explosion, whereas serious damage emerged in the joints of beam-column under internal explosion, besides failure in beam and column components. (2) After the internal explosion at the corner area of the RC frame structure, the risk of the progressive collapse of the RC frame structure increase if the corner column and its adjacent side columns fail at the same time. (3) The columns and the joints near the explosion position were seriously damaged after the internal explosion. Because many load transfer paths exist in the RC frame structure, partial collapse may incur the progressive collapse of the RC frame structure owing to the internal force redistribution. (4) Numerical simulation can well predict the dynamic disaster process of the RC frame structure under corner explosion. This method can provide reference for the further studies on the parameter analysis and the progressive collapse mode control of RC frame structures under blast loading.