New data from Neogene strata in northern South America suggest that Miocene tectonism in the northeastern Andes was responsible for the genesis of the Amazon River and changes in the drainage patterns of other major rivers such as the Magdalena and the Orinoco. Here we present a new model for the paleogeographic evolution of northern South America during the Miocene. In the early Miocene, a large part of the drainage of northwest Amazonia was directed northward along the paleo–Orinoco river system to a delta in Lake Maracaibo. Uplift of the Eastern Cordillera in the late middle Miocene caused the first development of the Amazon River; however, no connection with the Atlantic was established, and the Amazon fed the paleo–Orinoco river system, which drained toward the Caribbean. Substantial Andean uplift in the late Miocene resulted in major changes in paleogeography: the Orinoco changed its course, the Amazon established a connection to the Atlantic, causing the drowning of carbonate platforms, and the Amazon–Caribbean connection was closed. Thus the drainage and paleogeography of northern South America in the Miocene were strongly controlled by tectonic movements in the northeastern Andes.