The integration of drainage analysis and topographic metrics provides excellent tools to assess the Quaternary tectonic activity modeling landscape evolution in evolving orogens. Furthermore, detecting active structures through the geomorphological analysis of landscapes helps to identify potentially seismogenic structures that could impact the socio-economic conditions in developing countries. Therefore, this paper presents a tectonic geomorphology study conducted on the Santander Massif (SM, Colombian Eastern Cordillera) and surrounding areas. The SM has structures with reported Quaternary activity such as the Bucaramanga, Morro Negro-Las Mercedes, and Chitagá faults, which summed to a poorly-constrained paleosismological history with significant shallow events is the prime incentive of this work. Our study is based on the acquisition of topographic data through swath profiles, local relief, slope variability, filtered topography, minimum bulk erosion, which along with geomorphic indices like the normalized concavity steepness (ksn), the hypsometric integral (HI), the ratio valley floor width to valley height (Vf) and normalized river profiles provided new insights on the recent landscape evolution in this part of the Northern Andes.We compared published apatite fission tracks (AFT) data for the study area with the uplift pattern deciphered from the geomorphic indices to detect the consistency in exhumation and denudation processes both in the long and short-term. Consequently, the central SM, as well as the faulted block between the Bucaramanga and Guamalito faults, evidence a highly-incised landscape with local relief values exceeding the 1500 m, then, responding with a sharp incision to recent surface uplift. Interestingly, this uplift pattern in central SM matches with published AFT data and is related to Neogene exhumation events controlled by secondary structures like the Suratá Fault. We attribute this exhumation event, and accelerated denudation rates within the SM, to the influence exerted by the “collision” between the SM and the Pamplona Indenter, leading to the unroofing of basement rocks at the deformation front (e.g., the Vetas High) and the topographic building of the range.For the upthrown block (hanging wall) of the Bucaramanga Fault, the occurrence of poorly-graded river profiles with an average concavity factor of 12.01, as well as irregular hypsometric curves with convex lower reaches, reinforce the hypothesis that late Cenozoic topographic rejuvenation in the SM was also forced by the tectonic activity of the Bucaramanga Fault. We expect empirical uplift rates >0.08 mm/yr (very high to high tectonic activity) for the mountain front encompassed between La Esperanza and Bucaramanga localities. We state this assumption since the mountain front delimited by the structure mentioned above is quite straight, it preserves remarkable morphostructural features and displays V-shaped valleys with an average Vf index of 0.38. This uplift rate is in good agreement with recent thermochronological exhumation rates (0.1 to > 0.3 mm/yr) published by Siravo et al. (2019).Higher uplift rates associated with the Bucaramanga Fault were also constrained with the erosion proxy index, i.e., the ksn index. High ksn values (above 128) were observed following a linear pattern, which in turn seems controlled by the main trace of the Bucaramanga Fault. For instance, the river system draining the western piedmont of the SM, near Aguachica, records slope-break knickpoints that we interpret as evidence of an incisional wave migrating upstream and adjusting a late Neogene uplift event associated with the Bucaramanga Fault. Conversely, the northern SM presents variable tectonic activity with the inner part, east of the Guamalito Fault, presenting low tectonic activity with little surface uplift and dominant strike-slip kinematics. We recognize the Ocaña-Ábrego zone as a relict landscape with well-preserved non-consolidated deposits that may record the initial exhumation and denudational pulses of the SM during the Andean Orogeny.