Surface and subsurface data support a kinematic reconstruction of Cenozoic fold‐thrust deformation along the Eastern Cordillera‐Magdalena Valley transition in Colombia. The La Salina fault (LSF) marks the boundary between west‐vergent Eastern Cordillera structures and hinterland deposits of the Middle Magdalena Valley basin. Apatite fission track and (U‐Th)/He thermochronological results for the west‐directed LSF reveal initial hanging wall exhumation during middle Eocene–early Oligocene (45–30 Ma) shortening, renewed exhumation in the early middle Miocene (18–12 Ma), and accelerated late Miocene‐Pliocene (12–3 Ma) exhumation. Vitrinite reflectance data suggest maximum burial of 4–6 km, helping constrain Cenozoic basin architecture. Mapping of the LSF reveals hanging wall Cretaceous–Eocene rocks in a broad anticline‐syncline pair with limited faulting and footwall Eocene–Quaternary basin fill in a complex series of tight thrust‐related folds. Limited displacement along the westernmost (frontal) thrust suggests that shortening is largely accommodated by east‐directed thrusting within a broader triangle zone of a passive‐roof duplex (and probable minor strike‐slip deformation). In the preferred kinematic restoration, the most recent phase of shortening to transpressional deformation represents out‐of‐sequence reactivation of the LSF consistent with irregular crosscutting relationships among footwall structures. Earliest exhumation by 45–30 Ma in the Eastern Cordillera fold‐thrust belt is correlated with increased sedimentary lithic fragments and high compositional maturity in sandstones of the adjacent Magdalena Valley basin. Exhumation since ∼15 Ma coincided with decreased compositional maturity and elevated accumulation rates for the Real Group. The compositional provenance shifts are attributed to westward advance of fold‐thrust deformation into the proximal (eastern) segments of the Magdalena Valley basin.