This study proposes a new structural design of the first-story isolation system in reinforced concrete (RC) structures. Compared to the conditional buildings with independent columns, this new design integrates the independent columns with beams to increase the seismic capacity of the building by increasing the integrated stiffness of the coupled columns and the stability of the isolation system. The seismic responses of the proposed structure and the corresponding isolation effect were investigated by performing a series of numerical simulation and shaking table tests on a typical 7-story RC frame structure. The structure models were subjected to four earthquake waves with two PGAs (peak ground acceleration) of 0.30 g and 0.40 g for seismic analysis regarding the peak acceleration and inter-story displacement. Both simulation and testing results showed that the story acceleration and inter-story displacement of the superstructure in the isolated model decreased significantly. While the substructure below the isolation layer had a negligible decrease of acceleration. The connection of beams with concrete columns significantly increases the seismic capacity of the RC frame buildings compared to non-isolated frame buildings. The coupled beam-column connections could thus be potentially adopted in the practical first-story isolation system to avoid the requirements of large column stiffness and large column size.