The topographically prominent Sierra Nevada de Santa Marta forms part of a faulted block of continental crust located along the northern boundary of the South American Plate, hosts the highest elevation in the world (∼5.75 km) whose local base is at sea level, and juxtaposes oceanic plateau rocks of the Caribbean Plate. Quantification of the amount and timing of exhumation constrains interpretations of the history of the plate boundary, and the driving forces of rock uplift along the active margin. The Sierra Nevada Province of the southernmost Sierra Nevada de Santa Marta exhumed at elevated rates (≥0.2 Km/My) during 65–58 Ma in response to the collision of the Caribbean Plateau with northwestern South America. A second pulse of exhumation (≥0.32 Km/My) during 50–40 Ma was driven by underthrusting of the Caribbean Plate beneath northern South America. Subsequent exhumation at 40–25 Ma (≥0.15 Km/My) is recorded proximal to the Santa Marta-Bucaramanga Fault. More northerly regions of the Sierra Nevada Province exhumed rapidly during 26–29 Ma (∼0.7 Km/My). Further northward, the Santa Marta Province exhumed at elevated rates during 30–25 Ma and 25–16 Ma. The highest exhumation rates within the Sierra Nevada de Santa Marta progressed toward the northwest via the propagation of NW verging thrusts. Exhumation is not recorded after ∼16 Ma, which is unexpected given the high elevation and high erosive power of the climate, implying that rock and surface uplift that gave rise to the current topography was very recent (i.e., ≤1 Ma?), and there has been insufficient time to expose the fossil apatite partial annealing zone.