NW Iran, situated between the Arabian and Eurasian plates, carries a record of both Paleo-Tethyan and Neo-Tethyan tectonic evolution. During the Wilson Cycle of Tethys Ocean opening and closing, several episodes of magmatism from Late Paleozoic to latest Cenozoic generated a massive volume of intrusive rocks. These intrusives, which record cooling histories from high-temperatures to final exhumation, are ideal for multiple geo-thermochronological studies. Our new zircon and apatite U-Pb results suggest three regional magmatic events in the Late Carboniferous, mid-Cretaceous and middle Eocene, which could be related to Paleo-Tethys subduction, Neo-Tethys subduction and Neo-Tethyan ridge subduction, respectively. New apatite fission track and (U-Th)/He data reveal post-magmatic cooling and differential exhumation related to subduction and collision. By integrating published regional thermochronological data from northeastern part of the Middle East, a broader tectono-thermal framework is outlined as follows: 1) Cretaceous cooling signals are most pronounced in the Alborz and Caucasus, and reflect back-arc extension during Neo-Tethyan subduction; 2) diachronous Neo-Tethyan evolution led to the Paleocene assemblage of Anatolia in the west, and subduction associated with a late Paleocene-Eocene magmatic flare-up in Iran. Subsequent westward escape of Anatolia and extensive surface uplift were driven by propagation of Arabia-Eurasia collision in the Miocene; 3) Continuous northward indentation of Arabia into Eurasia triggered late Miocene-Pliocene fast exhumation of the Zagros, Alborz and the Caucasus. •U-Pb data reveal three magmatic episodes in NW Iran at ∼320, ∼ 100 and ∼ 40 Ma.•Thermochronological data record post-magmatic cooling and differential exhumation.•Miocene Arabia-Eurasia collision activated uplift and westward escape of Anatolia.•Arabia indentation triggered rapid exhumation in Eurasia interior since ∼10 Ma.