The purpose of this paper is to assess the influence of soil-structure interaction and site effects on the seismic behavior of steel moment-resisting frames, with a view to describing the underlying “physics” behind the damage mechanisms triggered. We examine an idealized 2-story, 1-bay steel frame under various earthquake recordings and intensity levels, as well as different subsoil and foundation conditions. The story drift ratio distribution and the moment-rotation response, at the beam and column ends, are indicatively presented and discussed, setting the benchmark for future research. In the cases examined, soil-structure interaction leads to increased drift demands in the first story, while the flexural demands at the fixed end column reduce due to the induced soil flexibility, accompanied by higher inelastic demands at the first-floor steel beams.