The Uzbek Tian Shan is a prominent metal-rich belt, hosting world-class orogenic Au deposits such as Muruntau. However, its post-collisional history in relation to fluid alteration and mineralisation remains elusive. We present apatite U–Pb dates and rare earth element geochemistry for 44 granitoids, revealing a prolonged history of low-grade metamorphism and associated fluid alteration between ~285 and ~240 Ma. A resulting apatite U–Pb age interpolation map reveals two young anomalies that are interpreted as post-orogenic fluid circulation cells. In addition, the extent of Meso-Cenozoic denudation is presented using apatite fission track (FT) age data. In areas of good data coverage, the combined Apatite U–Pb and FT anomalies reveal a correlation with the locations of orogenic Au mineralisation. Although more data is required to further evaluate such correlation, our study illustrates that integrated multi-method apatite thermochronology and geochemistry may have the potential to become a novel viable tool for mineral exploration.