Deep-seated structures can exhume deep crustal rocks (>20 km), transmitting the signal of geodynamic processes from the subduction zone to the interiors of the continents. The role of deep-seated structures can be analyzed with low-temperature thermochronological dating techniques. However, studies coupling low-temperature thermochronology with structural geological analyses of the deformational style are not common in the Northern Andes. In this contribution, we present new apatite (AFT) and zircon (ZFT) fission-track data coupled with meso- and microstructural analyses to reveal the deformational and exhumation history of the Santander Massif (SM; Northern Andes) and the related cortical Bucaramanga strike-slip fault (BF). Samples for thermochronological analyses were collected along an elevation profile with a significant elevation difference of 2.4 km across the western flank of the SM, crossing the BF. The time-temperature history modeling of ZFT data reveals phases of prolonged residence in the zircon partial annealing zone from ∼125 to 94 Ma and a cooling phase related to an exhumation episode at around 25 Ma based on samples collected near the BF. Inverse modeling of AFT data reveals structurally-controlled Pliocene exhumation rates of 0.6–0.7 km/Myr mediated by the action of secondary faults. A shift in the deformation style resulting from the oblique interaction of the SM and Mérida Andes domain is interpreted as the main driver of the Pliocene exhumation. This deformation phase is observed in the fault damage zone, where evidence of brittle-ductile deformation was exhumed. Finally, we discuss the geodynamic implications of our thermochronological and structural analyses, contrasting local and more regional competing hypotheses (Pamplona Indenter vs. slab break-off of the Caribbean plate), which may explain the tectonic evolution of the northern part of the Eastern Cordillera and the SM in the Colombian Northern Andes.