The Irtysh shear zone (ISZ) is an important structure in the framework of the Central Asian Orogenic Belt (CAOB). It represents the site of final collision of Kazakhstan with Siberia during Hercynian times and records up to 1000 km of lateral displacement during subsequent reorganization in the CAOB edifice. We present new zircon U/Pb, apatite fission track and fault kinematic data along the ISZ and consequently derived its tectonic history with emphasis on its formation and reactivation episodes. Carboniferous (_340 320 Ma) zircon U/Pb ages were obtained for the syn- and post-collisional Kalba Narym intrusives, dating their emplacement in the framework of the Siberia Kazakhstan collision. During this period, the ISZ experienced an early brittle left-lateral, mainly transtensional stress regime. Late Carboniferous Early Permian post-collisional intrusives were emplaced and the stress regime changed to a late brittle regime, characterized by more compressional conditions, indicating rheological strengthening as a response to cessation of ductile shearing and cooling of the ISZ crust. Apatite fission track data and thermal history modeling reveal Late Cretaceous (_100 70 Ma) cooling of the ISZ basement rocks as a response to denudation of a bordering Late Mesozoic Altai orogen. After this denudation event, the tectonic activity ceased during the Late Mesozoic Early Cenozoic. A final step of cooling (from _25 Ma), exhibited by some of the thermal history models, may reflect reactivation of the ISZ and initiation of Cenozoic Altai mountain building. The Late Plio-Pleistocene phase of mountain building coincides with a new change in the Palaeostress field, characterized by minor transpressional, right-lateral shear conditions