Abstract Lithospheric-scale experiments integrated with restored crustal transects are used to study the evolution of the Central Segment (confined between the Rio Grande Fracture Zone to the south and the Chain Fracture Zone to the north) of the South Atlantic margin. The presence of crustal inhomogeneities, located within the Brazilian Santos and Campos basins, have been analysed and modelled in order to better understand their effects on the rift evolution and resulting structural architecture of the conjugate rifted margins. The results show that heterogeneities located within the lower crust can have a remarkable impact on the along-margin segmentation promoting articulated basins with horsts and grabens in response to a relative “strong” rheology, and focused and deeper basins related to a relatively “weak” rheology on the equivalent parts of the conjugate pairs. In particular, at the early-stage rift evolution the deformation is concentrated at the inner margin where, in the presence of a weak lower crust rheology, a main deep listric half-graben fault and associated thick and wedge-shaped syn-rift basin sequences are developed. A strong lower crust rheology, instead, gives rise to more planar, rotated, domino-type faulted basins with thinner sequences directly controlled by the individual fault-blocks. At the late-stage rift evolution, once the effects of the initial crustal rheology inhomogeneities are reduced due to the lithosperic thinning process, the outer margin records a late syn-rift sequence which shows comparable thicknesses for both cases of lower crust rheologies. This tectono-stratigraphic evolution of the rifting process gives rise to along-margin alterations in symmetry versus asymmetry of the width and structural architecture. The performed analogue modelling experiments also indicate that during the rifting evolution pieces of brittle mantle are preserved and could be elevated beneath the developed upper crustal structures, giving rise to complicated predictions for the along-margin heat-flow.