The thermal history of the Late Paleozoic granitoids of the Angara-Vitim batholith (ABB) was reconstructed using a multi-system approach including U/Pb, 40Ar/39Ar, and fission track dating methods. The rocks of the Barguzinsky and Chivyrkuysky complexes were studied at sites in the southwestern and northeastern parts of the batholith, as well as on the Svyatoy Nose Peninsula and the eastern shore of Lake Baikal. The similar thermal history is reconstructed for the rocks of all sites as a whole. The steep position of the thermal history graph immediately after the formation of the ABB rocks indicates a major denudation epoch with an amplitude of about 7–5 km associated with the Late Paleozoic orogeny. After the epoch of tectonic stabilization, characterized by the time-stretched closure of the biotite isotope system, the closure of the feldspar/plagioclase isotope system occurs in the range of 170–140 Ma. This interval coincides with the closure of the Mongol-Okhotsk Ocean and the beginning of the formation of the orogen of the same name and is characterized by an amplitude of denudation of about 3 km. Further, in the period of 60–3 Ma, a slow denudation took place on the territory of Transbaikalia, which ended with a relatively sharp cooling of rocks during the last 3 Ma and denudation with an amplitude of about 3–2 km. This may be due to the long-range tectonic impact of the Indo-Eurasian collision. The obtained data on the tectonic-thermal evolution of AVB rocks can serve as a basis for identifying the relationship with the formation of the Mongol-Okhotsk orogen and sedimentation in the Jurassic-Early Cretaceous Irkutsk, Kansk-Achinsk, Tuva, Kuznetsk and West Siberian basins.