Abstract: A quasi-static test was carried out to experimentally study the progressive collapse of a two-story 2×1 bay spatial frame structure with slabs. The progressive collapse mechanism and deformation failure mode of the residual structure due to a side column loss were analyzed. The results indicate that the whole collapse resistance of RC frame structure is successively provided by beam arch-slab pressure membrane mechanism, beam arch-slab tensional membrane mechanism, beam catenary-slab tensional membrane mechanism and slab tensional membrane mechanism. The structural deformation process experiences three stages including the extrapolative stage, adductive stage and collapsed stage. The maximum resistance appears at a breaking point, which lies between stringing inward section and pushing outward section of the frame column (beam catenary-slab tensional membrane mechanism). The structure changes into a slab-column model when the beam is damaged, and the slab can maintain the resistance at a high level. The resistance and critical displacement at the key points of structural collapse are theoretically analyzed. A calculation method of structural ultimate load-bearing capacity is proposed. The ultimate load-bearing capacity and beam's rotation angle should be taken into consideration in the criteria for structural collapse.