The present-day configuration of the Lesser Caucasus and Eastern Pontides regions has been shaped by multiple episodes of arc magmatism, opening and closure of oceanic domains, obductions and collisions from the Paleozoic (~350–310 Ma) to Cenozoic (~50–20 Ma). This fascinating magmatic and tectonic evolution along these two adjacent regions was also associated with an exceptional metal endowment in the form of polymetallic deposits, volcanogenic massive sulfide deposits, porphyry Cu-Mo deposits and epithermal Cu-Au deposits in the Mesozoic and Cenozoic. Several decades of research have significantly improved our understanding of these two regions, yet conflicting models exist for the tectono-magmatic evolution of this orogenic belt. Here we present new zircon Hf isotopic data (n = 575) for magmatic rocks formed in the Lesser Caucasus at Kapan (136–16 Ma, 51 Ma), Gedabek (138–158 Ma), Tsaghkuniats (530 Ma, 320 Ma, 136–153 Ma), Alaverdi (146–164 Ma) and Bolnisi (82–85 Ma, 52 Ma) districts, and in the Eastern Pontides at Elbeyli (74 Ma), Emeksen (78–79 Ma), Güzelyayla (80 Ma) and Ulutas-Ispir (128–129 Ma) districts. The new results are combined with a comprehensive compilation of igneous ages (n = 4560), zircon Hf isotopic compositions (n = 1466), bulk rock major and trace element (n = 1304–1647) and Sr and Nd isotopic compositions (n = 1079) for magmatic rocks formed along the Eastern Pontides and the Lesser Caucasus. These complementary datasets highlight three well-defined cycles of arc magmatism during the Mesozoic and Cenozoic between the two regions, which is characterized by comparable temporal and geochemical trends in the Middle Jurassic-Early Cretaceous and the Late Cretaceous cycles, whereas these trends are no longer similar in the Eocene-Miocene cycle. The new data also reveal that Carboniferous basement rocks in the Tsaghkuniats area have overlapping ages and zircon Hf data with Carboniferous basement in the northernmost Lesser Caucasus and Eastern Pontides. This may suggest the presence of a composite basement in the Lesser Caucacus made of southern Eurasian margin slivers rifted prior to Early Mesozoic and Gondwana-derived South Armenian block accreted to the southern Eurasian margin during the Late Mesozoic-Early Cenozoic. This regional synthesis of the geochemistry of arc magmatism across the Lesser Caucasus and Eastern Pontides over time offers new additional petrological constraints and allows to support our model for the geodynamic evolution of the region. Building on this regional geodynamic framework, the spatial and temporal distribution of ore deposits provides important pieces of information regarding key factors, such as long-lived arc magmatism and switch of tectonic stress regime, controlling arc magma fertility, which ultimately offers new perspectives for exploration opportunities in the middle section of the Tethyan metallogenic belt.