This paper is concerned with the assessment of seismic drift demands in steel moment frames designed to comply with Eurocode 8 provisions, with due account for cyclic and in-cycle degradation. In addition to degradation effects, the main parameters examined include the ground motion frequency content as well as the level of constant relative strength or inelasticity. To represent a wide range of structural characteristics, a set of 54 multi-storey frames are considered, in which the number of stories, steel profiles, seismic hazard and compliance criteria are varied. Detailed incremental dynamic analyses are performed on the full set of frames using a suite of 56 far-field ground motion records, which are scaled appropriately to achieve different levels of inelastic demand or equivalent behaviour factors. The seismic performance is evaluated in terms of maximum global and local drifts as well as beam chord rotations. Characteristic results show that maximum response in terms of global deformations and inter-storey drifts is significantly affected by degradation phenomena, along with the ground motion frequency content and the level of inelastic demand. For medium rise typologies subjected to earthquakes with relatively high frequency content, concentration of seismic demand in terms of inter-storey drift is captured by the degrading models and leads to early development of plastic mechanisms. The seismic demand scenarios used in this study, through spectral acceleration-based scaling of ground motions, indicate that the influence of degradation can be significant not only at collapse levels but also at those associated with typical design situations. Finally, based on the extensive analyses carried out in this investigation, expressions for predicting the global and local demands are proposed and discussed.