Soil conditions have a great deal to do with damage to structures during earthquakes. Hence the investigation on the energy transfer mechanism from soils to buildings during earthquakes is critical for the seismic design of multi-story buildings and for upgrading existing structures. Thus, the need for research into soil–structure interaction (SSI) problems is greater than ever. Moreover, recent studies show that the effects of SSI may be detrimental to the seismic response of structure and neglecting SSI in analysis may lead to un-conservative design. Despite this, the conventional design procedure usually involves assumption of fixity at the base of foundation neglecting the flexibility of the foundation, the compressibility of the underneath soil and, consequently, the effect of foundation settlement on further redistribution of bending moment and shear force demands. Hence the SSI analysis of multi-story buildings is the main focus of this research; the effects of SSI are analyzed for typical multi-story building resting on raft foundation. Three methods of analysis are used for seismic demands evaluation of the target moment-resistant frame buildings: equivalent static load; response spectrum methods and nonlinear time history analysis with suit of nine time history records. Three-dimensional FE model is constructed to investigate the effects of different soil conditions and number of stories on the vibration characteristics and seismic response demands of building structures. Numerical results obtained using SSI model with different soil conditions are compared to those corresponding to fixed-base support modeling assumption. The peak responses of story shear, story moment, story displacement, story drift, moments at beam ends, as well as force of inner columns are analyzed. The results of different analysis approaches are used to evaluate the advantages, limitations, and ease of application of each approach for seismic analysis.