Northern South America experienced significant changes in drainage patterns during the opening of the South Atlantic Ocean. Disappearance of a mega-wetland in the western Amazonian basins was followed by the formation of the eastward-draining Amazon River, which has been attributed to Andean uplift [1][2][3][4][5] . However, South America's westward motion over cold, dense subducted slabs implies that regional subsidence and uplift east of the Andes may have been driven by mantle convection. Here we use a coupled model of mantle convection and plate kinematics to show that dynamic subsidence of up to 40 m Myr . The resulting progressive tilt of northern South America to the east enabled the establishment of the Amazon River, suggesting that mantle convection can profoundly affect the evolution of continental drainage systems.During the Early Miocene (from ∼23 Myr bp), an inland fluviolacustrine/marginally marine Amazonian system partially flooded northwest South America with regional drainage mainly northwards towards the Caribbean 1-4 . This Amazonian megawetland existed at least from the Middle to Late Miocene 1,2 when the dominant fluvial drainage switched to its present course towards the Atlantic. This shift, initiating the fluviolacustrine system that is now the Amazon River is supported by sediment provenance, palaeo-transport direction and biostratigraphic studies [1][2][3]5 . The timing of this onset is estimated from offshore sedimentary records between 10.6 and 9.7 Myr bp (ref. 6). Any possible AmazonianCaribbean connection was fully closed by the Late Miocene 2 , with the Amazon River reaching its present shape and size from the Pleistocene onwards 2,7 (∼2.4 Myr bp). During the Early and Middle Miocene a restricted eastward-flowing palaeo-Amazon River may have drained to the Atlantic coast 7 . Stratigraphic data suggest that this fluvial system extended westward until limited by the Purus arch 7 (Fig. 1), a structural high that separated the Solimões and Amazonas basins and restricted the Amazonian mega-wetland to the west and the palaeo-Amazon River to the east.The main Miocene changes in drainage patterns, and the formation of the Amazon River, are commonly attributed to uplift in the northwest Andes 5,[8][9][10][11] . It has been proposed that the uplift of the Eastern Cordillera caused flexural subsidence in the foreland basins, and redirected a significant portion of the northwest Amazonas basin drainage, along the northward-flowing Palaeo-Orinoco and Magdalena rivers, to the east 2 . In addition, it has also been suggested that Amazon landscape evolution can be attributed to Early Tertiary to Holocene intraplate tectonics, including subsidence associated with a low-rate extension that contributed to a structural low 12 . The Late Miocene (∼11 Myr bp) is also well documented for a significant drop in sea level, which would have contributed to the disappearance of the Amazonian mega-wetland and marine incursions 13,14 , but could not have caused a fundamental change in the continental drainage pa...