New apatite fission-track data, paleoelevation estimates from paleobotany, and recently acquired geological data from the Eastern Cordillera of Colombia document the onset of increased exhumation rates in the northeastern Andes at ca. 3 Ma. The Eastern Cordillera forms an efficient orographic barrier that intercepts moisture-laden winds sourced in the Amazon lowlands, leading to high rainfall and erosion gradients across the eastern flank of the range. In contrast, the drier leeward western flank is characterized by lower rates of deformation and exhumation. In light of the geological evolution of the Eastern Cordillera, the combination of these data sets suggests that the orographic barrier reached a critical elevation between ca. 6 and ca. 3 Ma, which ultimately led to protracted, yet more focused erosion along the eastern flank. Sequentially restored structural cross sections across the eastern flank of the Eastern Cordillera indicate that shortening rates also have increased during the past 3 Ma. From fission-track and structural cross-section balancing, we infer that accelerated exhumation led to increasing tectonic rates on the eastern flank, creating a pronounced topographic and structural asymmetry in the Eastern Cordillera. The tectonic and climatic evolution of this orogen thus makes it a prime example of the importance of climatic forcing on tectonic processes.