The tropical Northern Andes of Colombia are one the world's most biodiverse places, offering an ideal location for unraveling the linkages between the geodynamic forces that build topography and the evolution of the biota that inhabit it. In this study, we utilize geomorphic analysis to characterize the topography of the Western and Central Cordilleras of the Northern Andes to identify what drives landscape evolution in the region. We supplement our topographic analysis with erosion rate estimates based on gauged suspended sediment loads and river incision rates from volcanic sequences. In the northern Central Cordillera, an elevated low-relief surface (2500 m in elevation, ~40 × 110 km in size) with quasi-uniform lithology and surrounded by knickpoints, indicates a recent increase in rock and surface uplift rate. Whereas the southern segment of the Central Cordillera shows substantially higher local relief and mostly well graded river profiles consistent with longer term uplift-rate stability. We also identify several areas of major drainage reorganization, including captures and divide migrations. These changes in the topography coincide with the proposed location of a slab tear and flat slab subduction under the northern Central Cordillera, as well as with a major transition in the channel slope of the Cauca River. We identify slab flattening as the most likely cause of strong and recent uplift in the Northern Andes leading to ~2 km of surface uplift since 8–4 Ma. Large scale drainage reorganization of major rivers is likely driven by changes in upper plate deformation in relation to development of the flat slab subduction geometry; however, south of the slab tear other factors, such as emplacement of volcanic rocks, also play an important role. Several biologic observations above the area of slab flattening suggest that surface uplift isolated former lowland species on the high elevation plateaus, and drainage reorganization may have influenced the distribution of aquatic species.