Late Cenozoic gneiss domes cover ∼30% of the surface of the Pamir salient in the northwestern end of the India−Asia collision zone. The highest peaks of the Pamir are in the east, where the ∼250-km-long, ∼N−S-trending Kongur Shan extensional system controls the topography. We combined 115 new apatite (U-Th-Sm)/He and zircon (U-Th)/He single-grain dates from 18 samples and previous thermochronologic data with three-dimensional thermokinematic models to constrain the thermo-tectonic history of the southern portion of the Muztaghata dome, one of the largest gneiss domes in the eastern Pamir. The new cooling dates from the western boundary of the southern Muztaghata dome generally increase with distance from the southern Kongur Shan fault and are related to normal faulting along the fault at near-surface levels over the last 6.5 m.y. The new dates across the central−eastern portion of the dome outline the previously recorded U-shaped date pattern at a higher spatial resolution. The modeling indicates that this pattern is most likely the result of uplift and erosion above a flat-ramp-flat thrust fault at depth over the last 7 m.y. Modeling does not resolve how topographic changes may have affected the observed distribution of cooling dates, but it indicates a faster thrust-slip rate associated with an increase in relief and a slower one associated with steady-state topography. Our results suggest that the modern topography along the southern Muztaghata dome, similar to the rest of the eastern Pamir salient, is shaped by normal faulting at shallow depth, but its growth may still be governed by contraction and crustal thickening at depth.