The nonlinear-inelastic response of reinforced concrete moment-resisting frame buildings due to an adjacent excavation in soft to medium clays is presented. An advanced numerical model is used to account for building-soil-excavation interactions, post-yielding behavior of the structural members, and solid-fluid coupled behavior of supporting soils. The effects of the excavation on the internal force redistributions of structural members, lateral and vertical distortions, ground surface settlements, and lateral wall movements are presented in terms of angular distortions and drifts, curvature ductility, axial forces, and flexural moments. Results showed how beams progressively developed plastic deformations as deep-seated movements occurred during the excavation of soft and medium clays, reaching maximum curvature ductility ratios larger than 2. As the excavation advanced, maximum curvature ductilities of up to 5 were computed in beams closer to the excavation, causing localized inelastic mechanisms in the building. This paper shows how even well-designed buildings to withstand large levels of lateral load demands using strong column–weak beam approaches can still be subjected to significant excavation-induced nonlinear-inelastic demands that can cause damage.