This study aims to better understand the seismic responses and isolation effect of a first-story, independent, column-top isolation structure with concrete frames. A series of shaking table tests and a numerical simulation were performed on a seven-story reinforced concrete–framed structure with first-story isolation, using rubber bearings. A non-isolated, structural model was used as a reference for comparison. The testing and numerical results showed that the story acceleration and inter-story displacement of the superstructure in the isolation model were significantly reduced, indicating the good damping effect of the isolation system. This system, which composed of rubber bearings, could absorb most of the seismic energy. The inter-story displacement of the substructure in the isolation model was also significantly reduced, while the acceleration was slightly reduced. The horizontal deformation of the column was not severe, and the seismic capacity of the substructure was higher than that of the superstructure. It is suggested that to guarantee the seismic security of reinforced concrete–framed structures with the first-story column-top isolation under extremely rare strong earthquakes, the stiffness of columns in the substructure should be further strengthened. Moreover, it is effective and reasonable to adopt the first-story column-top isolation method to improve the seismic capacity of reinforced concrete–framed structures with a weak first story.