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 morphological contrast between the low relief Altiplano and the high relief Eastern Cordillera makes this area a well suited place to determine spatiotemporal 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 four altitudinal profiles and additional individual samples. Age-elevation relationships and thermal modeling both document that the Abancay Deflection experienced a moderate, spatially uniform, and steady exhumation at 0.2 ± 0.1 km/Myr between 40 and ∼5 Ma implying common large scale exhumation mechanism(s). 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/Myr). This differential exhumation since ∼5 Ma implies active tectonics, river capture, and incision affecting the southern Eastern Cordillera. 3D thermokinematic 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 protosyntaxis, similar to the syntaxes described in the Himalaya or Alaska.