Central Iran provides an ideal region in which to study the long-term morphotectonic response to the nucleation and propagation of intraplate faulting. In this study, a multidisciplinary approach that integrates structural and stratigraphic field investigations with apatite (U + Th)/He (AHe) thermochronometry is used to reconstruct the spatio-temporal evolution of the Kuh-e-Faghan Fault in northeastern central Iran. The Kuh-e-Faghan Fault is a narrow, ∼80-km-long, deformation zone that consists of three main broadly left-stepping, E-W–trending, dextral fault strands that cut through the Mesozoic–Paleozoic substratum and the Neogene–Quaternary sedimentary cover. The AHe thermochronometry results indicate that the intrafault blocks along the Kuh-e-Faghan Fault experienced two major episodes of fault-related exhumation at ca. 18 Ma and ca. 4 Ma. The ca. 18 Ma faulting/exhumation episode is chiefly recorded by the structure and depositional architecture of the Neogene deposits along the Kuh-e-Faghan Fault. A source-to-sink scenario can be reconstructed for this time frame, where topographic growth caused the synchronous erosion/exhumation of the pre-Neogene units and deposition of the eroded material in the surrounding fault-bounded continental depocenters. Successively, the Kuh-e-Faghan Fault gradually entered a period of relative tectonic quiescence and, probably, of regional subsidence, during which a thick pile of fine-grained onlapping sediments was deposited. This may have caused resetting of the He ages of apatite in the pre-Neogene and the basal Neogene successions. The ca. 4 Ma faulting episode caused the final exhumation of the fault system, resulting in the current fault zone and topography. The two fault-related exhumation episodes fit with regional early Miocene collision-enhanced uplift/exhumation, and the late Miocene–early Pliocene widespread tectonic reorganization of the Iranian Plateau. The reconstructed long-term, spatially and temporally punctuated fault system evolution in intraplate central Iran during Neogene–Quaternary times may reflect states of far-field stress changes at the collisional boundaries.