The aim of this study is to investigate the effects of variable axial loads caused by horizontal and vertical ground motions on the seismic performance of reinforced concrete columns. First, three groups of cyclic loading tests were conducted. Further, the effects of constant axial load, axial load amplitude variation and frequency variation on the seismic performance indicators of the specimens, such as the failure mode, hysteresis curve, skeleton curve, stiffness degradation, ductility and energy dissipation, were studied. Subsequently, numerical analysis models were established using fiber finite elements, and verified their accuracies using experimental data. Finally, parametric analyses were conducted based on the verified numerical models to examine the effects of variable axial loads with different amplitudes, frequencies and phases on the columns. The results indicate that the axial load ratio of the columns changes constantly under the variable axial load, which results in readily apparent asymmetry in the hysteresis curve, ductility, and ultimate load. The hysteresis behavior of columns under variable axial load mainly depends on the axial load ratio corresponding to the positive and negative peak lateral drifts of each cycle. An equivalent axial load ratio method is proposed to determine the hysteresis model of columns under variable axial loads accurately.