The Altai Mountains form an intracontinental, transpressive deformation belt in the NW Central Asian orogenic system. Using a multi-method chronometric approach, the thermo-tectonic history of the basement underlying the Teletskoye graben area is constrained in more detail. The results provide new insights into the Siberian Altai basement evolution from the Early Palaeozoic to the present. Zircon SHRIMP (sensitive high-resolution ion microprobe) U–Pb ages (Late Ordovician–Early Silurian, 460–420 Ma) indicate an earlier crystallization age for the basement granitoids than previously thought (Late Devonian–Early Carboniferous, 370–350 Ma), while new multi-mineral ⁴⁰Ar/³⁹Ar age spectra suggest continuous basement cooling throughout the Devonian–Carboniferous. Reactivation of long-lived Palaeozoic structures controls the Teletskoye graben formation since the Plio-Pleistocene as a distant effect of India–Eurasian convergence. Deformation is propagated through Central Asia and Siberia along an inherited structural network closely associated with its basement fabric. A similar reactivation affected the Altai during the Mesozoic. Modelled apatite fission-track data suggest Late Jurassic–Cretaceous (150–80 Ma) cooling, interpreted to be related to denudation and the tectonic reactivation that we link to the coeval Mongol–Okhotsk orogeny. From the Late Cretaceous until the Pliocene, the thermal history models indicate a period of stability. Roughly around 5 Ma ago renewed cooling is observed that possibly represents the denudation and growth of the present-day Altai, and provides the context for the Teletskoye graben formation. A modelled Late Cenozoic cooling can be a result of, or overemphasized by, a modelling artefact. Some caution should be taken not to overinterpret this cooling phase.