The axial force will be altered as a result of the overturning influence exerted by both horizontal and vertical seismic events, as well as the secondary effects induced by gravitational loads. The variation of the axial force will greatly affect the seismic performance of reinforced concrete (RC) columns, thus warranting close attention. This paper proposes a hysteresis model of RC columns considering the cumulative damage effect under the action of variable axial force. First, three groups of cyclic loading tests were performed across three distinct groups. Subsequently, numerical analysis models were constructed, employing fiber-based finite element methods. Furthermore, according to the test and finite element simulation results, the existing damage value was modified to describe the degradation of the stiffness and load-bearing capacity. Next, through a regression analysis, the skeleton curve was established. Finally, the hysteresis behavior under the influence of variable axial load was ascertained. The results, when compared with the experimental data, show that the proposed hysteresis model can accurately describe the seismic performance of RC columns under the influence of variable axial force.