We investigate the evolution of the Iberia–Newfoundland margin from Permian post-orogenic extension to Early Cretaceous break-up. We used a Quantitative Basin Analysis approach to integrate seismic stratigraphic interpretations and drill-hole data of two representative sections across the Iberia–Newfoundland margin with kinematic models for lithospheric thinning and subsequent flexural readjustment. We model the distribution of extension and thinning, palaeobathymetry, crustal structure, and subsidence and uplift history as functions of space and time. We start our modelling following post-orogenic extension, magmatic underplating and thermal re-equilibration of the Permian lithosphere. During the Late Triassic–Early Jurassic, broadly distributed, depth-independent lithospheric extension evolved into Late Jurassic–Early Cretaceous depth-dependent thinning as crustal extension progressed from distributed to focused deformation. During this time, palaeobathymetries rapidly deepened across the margin. Modelling of the southern and northern profiles highlighted the rapid development of crustal deformation from south to north over a 5–10 myr period, which accounts for the rapid change in Tithonian–Valanginian, deep- to shallow-water sedimentary facies between the Abyssal Plain and the adjacent Galicia Bank, respectively. Late-stage deformation of both margins was characterized by brittle deformation of the remaining continental crust, which led to exhumation of subcontinental mantle and, eventually, continental break-up and seafloor spreading.