Abstract The Zangezur-Ordubad mining district of the southernmost Lesser Caucasus is located in the central segment of the Tethyan metallogenic belt and consists of porphyry Cu-Mo and epithermal Au and base metal systems hosted by the composite Cenozoic Meghri-Ordubad pluton. Ore-hosting structures and magmatic intrusions are predominantly confined to a central N-S–oriented corridor 40 km long and 10 to 12 km wide, located between two regional NNW-oriented right-lateral faults, the Khustup-Giratagh and Salvard-Ordubad faults. The anatomy and kinematics of the main fault network are consistent with dextral strike-slip tectonics controlled by the NNW-oriented Khustup-Giratagh and Salvard-Ordubad faults. Dextral strike-slip tectonics was initiated during the Eocene, concomitantly with final subduction of the Neotethys, and controlled the emplacement of the Agarak, Hanqasar, Aygedzor, and Dastakert porphyry Cu-Mo and Tey-Lichkvaz and Terterasar epithermal Au and base metal deposits. The Eocene structures were repeatedly reactivated during subsequent Neogene evolution in transition to a postsubduction geodynamic setting. Ore-bearing structures at the Oligocene world-class Kadjaran porphyry Cu-Mo deposit were also controlled by dextral strike-slip tectonics, as well as porphyry mineralization and its epithermal overprint hosted by an early Miocene intrusion at Lichk. Eocene to early Miocene dextral strike-slip tectonics took place during NE- to NNE-oriented compression related to Paleogene Eurasia-Arabia convergence and subsequent Neogene postcollision evolution. Paleostress reconstruction indicates major reorganization of tectonic plate kinematics since the early Miocene, resulting in N-S– to NW-oriented compression. Early Miocene epithermal overprint at the Kadjaran porphyry deposit and left-lateral reactivation of faults and mineralized structures are linked to this late Neogene tectonic plate reorganization.