The Pamir Plateau contains critical information on the tectonic evolution of the Tethys domain. In this study, we report geochronology, geochemistry, and Sr-Nd-Hf isotopic compositions of the Cenozoic adakitic monzogranite in the Reskam and Taxkorgan areas, NE Pamir, to provide new insights into the post-collisional tectonic evolution following the India-Eurasian collision. Zircon UPb ages reveal these granitoids were emplaced at ca 12–8 Ma. Geochemically, they exhibit relatively uniform whole-rock major and trace element compositions, and share typical adakitic signatures with high SiO2 (68.55–73.30 wt%), moderate Al2O3 (14.11–15.84 wt%), elevated Sr (399–1710 ppm) and La (34–182 ppm), but low Y (5.53–15.10 ppm) and Yb (0.39–1.26 ppm), and thus in high Sr/Y (32−200) and (La/Yb)N ratios (20–236). Isotopically, these adakitic rocks show significantly enriched whole-rock SrNd (εNd(t) = −7.97 to −5.76; 87Sr/86Sr(t) = 0.7072–0.7110) and zircon Hf (mostly εHf(t) -5 to −2) isotopic compositions. Elemental and isotope signatures indicate their origin from partial melting of mafic-intermediate sources under high pressure, with a residuum of negligible feldspar but dominant garnet. Integrating the new findings with reported data of granitoids in the Pamir, we estimate the crustal thickness variations from the Cretaceous to Miocene. The crustal thickness in the Pamir region largely remained no more than 45 km before India-Asia collision, after which a significant increase in crustal thickness occurred, reaching a peak of 80–100 km around 10 Ma. We propose that the break-off of the subducted Neo-Tethys oceanic slab (ca. 40 Ma) and lithospheric delamination (ca. 25 Ma) led to two-stage rapid continental uplift events in Pamir Syntax.