The Magdalena River, a major fluvial system draining most of the Colombian Andes, is a world-class river, in the top 10 in terms of sediment load (≈150 MT/yr). In this study, we explore the major natural factors and anthropogenic influences behind the patterns in sediment yield on the Magdalena basin and reconstruct the spatial and temporal pattern of deforestation and agricultural intensification across the basin to test the relationships between land use change and trends in sediment yield. Our results show that sediment yield for the whole Magdalena catchment can be explained by natural variables, including runoff and maximum water discharge. These two estimators explain 58% of variance in sediment yield. Temporal analyses of sediment discharges and land use show that the extent of erosion within the catchment has increased over the last 10 to 20 years. Many anthropogenic influences, including a forest decrease by 40% in a 20-year period, an agriculture and pasture increase by 65%, poor soil conservation and mining practices, and increasing rates of urbanization, may have accounted for the overall increasing trends in sediment yield on a regional scale.