Multi-method thermochronology along the Vakhsh-Surkhob fault zone reveals the thermotectonic history of the South Tian Shan–Pamirs boundary. Apatite U/Pb analyses yield a consistent age of 251 ± 2 Ma, corresponding to cooling below ~550–350°C, related to the final closure of the Palaeo-Asian Ocean and contemporaneous magmatism in the South Tian Shan. Zircon (U–Th–Sm)/He ages constrain cooling below ~180°C to the end of the Triassic (~200 Ma), likely related either to deformation induced by the Qiangtang collision or to the closure of the Rushan Ocean. Apatite fission track thermochronology reveals two low-temperature (<120°C) thermal events at ~25 Ma and ~10 Ma, which may be correlated with tectonic activity at the distant southern Eurasian margin. The late Miocene cooling is confirmed by apatite (U–Th–Sm)/He data and marks the onset of mountain building within the South Tian Shan that is ongoing today.