In this paper, a series of inelastic transient analysis of steel frame structures under blast loads are numerically performed. Considering the coupling actions of detonator, gases and structure, Arbitrary Lagrangian Eulerian ALE method which is suitable for large deformation systems is applied. In order to capture the effect of explosion load on members, a rate-dependent stress–strain model is used to model the material response of the affected members. The dynamic response and the structural damage of steel frame under blast loading are investigated. The damage pattern of steel frame to blast loads is studied. The results show that the permanent deformation, local buckling, and plastification reduce the resistance of the frame. The affected members may trigger the overall stability of the frame. The damage degree is related to the amount and position of explosives, shape and resistance of the building etc. The damage of the low-story columns and beams may make the structure unstable. The load might not be large enough, the damage to the entire frame may be severe, and it may cause structure collapse.