Deforestation changes the hydrological, geomorphological, and biochemical states of river systems by decreasing evapotranspiration and increasing runoff and river discharge across all spatial scales. Increased runoff and decreased vegetative cover increase erosion and alter river and floodplain morphology as sediments are deposited in side channels and bars. However, attribution of such changes in large rivers is difficult, because deforestation often takes place before instrumentation has begun and is coincident with other human alterations of the river channel, such as the construction of dams and levees. Here we show that deforestation that began in the 1960s in the savannah region of central Brazil (locally know as Cerrado) has altered 62% of the landscape and has significantly altered the morphological and hydrological characteristics of a 120,000km2 watershed of the otherwise unmodified Araguaia River. Fieldwork and imagery analysis show a 28% increase in sediment transport, 188 million tons of stored sediment, and an increase in the number of sandy bars but a decrease in the number of islands since the 1960s. Observed discharge increased by 25% from the 1970s to the 1990s and simulations with a land surface vegetation and hydrology model indicate that about 2/3 of the increase may be from deforestation. These results provide the first unequivocal quantification of human alterations of the hydrology and geomorphology of a large tropical river. Further, they suggest that similar changes have occurred throughout the 2,000,000 km2, hydrologically important Cerrado region and that many other large tropical rivers are similarly affected by ongoing deforestation.