The retro-arc foreland Andean Amazon Basin records sedimentary infill from the South American craton and the emerging Northern Andean chain from the middle Cretaceous until Present day. The U/Pb ages of detrital zircons indicate significant reworking of Archean-Proterozoic (max. 2.9 Ga) and Paleozoic crust and sediments, which were eroded on both sides. Heavy mineral associations show that the material derived from Proterozoic craton was supplied by Cretaceous reworking of non-metamorphosed (unannealed) Paleozoic and older sedimentary rocks, which cover the Amazon Craton. Following latest Cretaceous switch of the dominant sediment source to the Andean cordillera, the influx of Precambrian zircons persisted, and these zircons were derived from the metamorphosed basement and Paleozoic sediments of the Cordillera Real (Loja terrane). Re-evaluation of existing detrital zircon fission-track record proves that the rise of the Cordillera Real at the Cretaceous-Tertiary transition was initiated by the collision of Caribbean Oceanic Plateau and associated arc elements from 75–65 Ma. A further important exhumation event also occurred in the Late Oligocene, which is correlated with the break-up of the Farallon plate.