Previous quantitative studies dealing with the origin of foreland basins have focused primarily either on the rheological basis of the lithosphere mechanical response or on the relationship between orogenic loading and sediment geometry. To link the evolution of the Guadalquivir foreland basin (South Iberia) with the thermomechanical stratification of the Iberian lithosphere, we combine quantitative approaches to deep and shallow processes: thrust loading, lithospheric flexure, thickness changes of the crust and the lithospheric mantle, and surface mass transport. A planform flexural analysis of the present-day load distribution shows that basement subsidence is related not only to upper crustal thrusting but also to a deep-seated additional load. On the basis of the observed gravity and geoid fields, we propose this additional load to be related to a lithospheric mantle thickening larger than the coeval crustal thickening. Further modeling of the evolution of a basin cross section reveals that the architecture of the sedimentary basin is additionally related to the lithosphere rheological response. The quantitative study of the evolution of basement faulting and the forebulge uplift of Sierra Morena leads us to conclude that viscous stress relaxation and/or plastic yielding within the lithosphere are key processes to explain the flexural evolution of the basin.