Abstract The Central Andes in Bolivia and northern Chile form part of a wide and obliquely convergent plate-boundary zone where the oceanic Nazca plate is being subducted beneath the continental South American plate. In the latest Cretaceous and Palaeocene, this part of the Central Andes formed a volcanic arc along what is today the forearc region of northern Chile, with a wide zone of subsidence, as much as 400 km wide, at or close to sea level behind the arc. In the Eocene, the central part of the behind-arc basin was inverted to form a zone of uplift (proto-cordillera), about 100 km wide and along what is today the western margin of the Eastern Cordillera of Bolivia. The Altiplano basin and an early foreland basin were initiated at this time, receiving sediment from the Eocene proto-cordillera. Subsequently, the proto-cordillera widened, as the rate of deformation increased and deformation spread westwards into the early Altiplano basin, and also eastwards towards the Brazilian Shield. In the Late Miocene, deformation essentially ceased in the Altiplano and Eastern Cordillera. An intense zone of shortening was initiated in what is today the Subandean Zone on the eastern margin of the Central Andes, deforming the Oligo-Miocene foreland basin. Shortening in the Subandean Zone accommodated both underthrusting of the Brazilian Shield and also bending of the entire mountain belt about a vertical axis. It is suggested that much of the distinctive Cenozoic tectonic evolution of this part of the Andes is related to pre-Andean strength inhomogeneities in the South American lithosphere.