The Shamlugh polymetallic deposit located in the Alaverdi mining district, Armenia is hosted by Middle Jurassic magmatic rocks of the Somkheto-Karabakh island arc, Lesser Caucasus. Lithogeochemistry and radiogenic isotope geochemistry indicate a subduction setting with an evolution from tholeitiic to transitional Middle Jurassic magmatism to calc-alkaline to high-K/shoshonitic Late Jurassic magmatism. A progressively more juvenile mantellic input in the magmatic source is noted. Ore consists of stratabound massive sulfide ore bodies, ore-bearing breccia, stockwork-style mineralization and disseminated ore hosted by a pyroclastic host rock unit below a subvolcanic rhyolitic sill. Towards depth, the stratabound ore is connected to subvertical high-grade sulfide veins hosted by basaltic andesitic, andesitic and dacitic tuff and lava breccia. Ore minerals include principally pyrite and chalcopyrite with minor sphalerite and hematite. Hydrothermal alteration consists of quartz, chlorite, carbonate and sericite in the footwall pyroclastic rock, tuff and lava breccia, which are also crosscut by late stage carbonate and barite veins. The rhyolitic sill has been affected by silicification and sericite alteration, and contains rare sulfides. Sulfur isotope values for sulfides range from +0.7 to +4.6 ‰, and suggest an essentially magmatic source for sulfur. Strontium isotopic compositions of hydrothermal carbonates and sulfates (0.70507 - 0.70660), sulfur isotopes of sulfates (+16.8 to +17.3 δ34S ‰ VCDT) and carbon and oxygen isotopic compositions of late stage carbonates (δ18O: +15.9 to +17.6 ‰ VSMOW; δ13C: -1.8 to -0.8 ‰ VPDB) are permissive with seawater incursion in the ore-forming hydrothermal system, but can also be attributed to fluid-rock interaction with hidden metamorphic basement rocks and Jurassic magmatic rocks. The lead isotopic composition of sulfides (206Pb/204Pb: 18.505 to 18.586, 207Pb/204Pb: 15.611 to 15.636, 208Pb/204Pb: 38.516 to 38.640) implies leaching of the Middle Jurassic host rocks as the main source of metals. LA-ICP-MS U-Pb zircon dating of the hanging wall rhyolitic sill affected by hydrothermal alteration yielded an age of 155.0 ± 1.0 Ma, and provides a maximum age for mineralization. Ore formation at Shamlugh is younger than the immediate Middle Jurassic host rocks and is related to the Late Jurassic calc-alkaline and high-K/shoshonitic magmatic evolution. Late Jurassic magmatism includes a tonalite dated by LA-ICP-MS U-Pb zircon geochronology at 152.9 ± 0.7 Ma that hosts the 146 Ma-old Teghout porphyry deposit. In the absence of other age constraints, the genetic relationship of the polymetallic Shamlugh deposit with the Teghout porphyry deposit remains open to question. Nevertheless, hydrothermal opaque mineral and alteration paragenesis, and the lithologically and structurally controlled ore body geometry at Shamlugh are consistent with a low to intermediate sulfidation epithermal model.