This paper examines the level of vertical irregularity and the influence of the frequency content of earthquakes on the vertically irregular reinforced concrete step-back, step-back–setback building frames. The regularity indices of these frames determined first to assess the level of irregularity and then the dynamic responses of the buildings under three distinct earthquakes of low, intermediate, and high-frequency contents are evaluated. It is noted that the irregularity of step-back frames is decreasing as the number of storeys increasing, whereas the irregularity of step-back–setback frames is increasing as the number of storeys and bays increasing. And the step-back frames are seismically responsible for low and medium frequency content earthquakes. In contrast, the step-back–setback frames are responsible for medium and high-frequency content earthquakes. The seismic vulnerability indices of these building frames are also determined and it is observed that there is rarely any correlation existed between the seismic vulnerability index, regularity index, and the influence of the earthquake frequency content.