Located at the northern tip of the Altiplano, the Abancay Deflection marks abruptly the latitudinal segmentation of the Central Andes spreading over the Altiplano to the south and the Eastern Cordillera northward. The striking contrast in terms of morphology between the low-relief Altiplano and the high-jagged Eastern Cordillera makes this area a privileged place to determine spatio-temporal variations in surface and/or rock uplift and discuss the latest phase of the formation of the Central Andes. Here, we aim to quantify exhumation and uplift patterns in the Abancay Deflection since 40 Ma, and present new apatite (U-Th)/He and fission-track data from five altitudinal profiles and additional individual samples. Age-Elevation relationships and thermal modeling both evidence that the Abancay Deflection experienced a moderate, spatially-uniform and steady exhumation at 0.2±0.1 km/m.y. between 40 Ma and ~5 Ma implying common large-scale exhumation mechanisms. From ~5 Ma, while the northern part of the Eastern Cordillera and the Altiplano registered similar ongoing slow exhumation, the southern part of the Eastern Cordillera experienced one order-of-magnitude of exhumation acceleration (1.2±0.4 km/m.y). This differential exhumation since ~5 Ma implies active tectonics, river capture and incision affecting the southern Eastern Cordillera. 3D thermo-kinematic modeling favors a tectonic decoupling between the Altiplano and the Eastern Cordillera through backthrusting activity of the Apurimac fault. We speculate that the Abancay Deflection, with its “bulls-eye” structure and significant exhumation rate since 5 Ma, may represent an Andean proto-syntaxis, similar to the syntaxes described in the Himalaya or Alaska.