Abstract Muruntau in the Central Kyzylkum desert of the South Tien Shan, western Uzbekistan, with past production of ~3,000 metric tons (t) Au since 1967, present annual production of ~60 t Au, and large remaining resources, is the world’s largest epigenetic Au deposit. The host rocks are the mainly Cambrian-Ordovician siliciclastic flysch of the Besapan sequence. The rocks were deformed into a broadly east-west fold-and-thrust belt prior to ca. 300 Ma during ocean closure along the South Tien Shan suture. A subsequent tectonic transition was characterized by left-lateral motion on regional splays from the suture and by a massive thermal event documented by widespread 300 to 275 Ma magmatism. The Besapan rocks were subjected to middle to upper greenschist-facies regional metamorphism, an overprinting more local thermal metamorphism to produce a large hornfels aureole, and then Au-related hydrothermal activity all during early parts of the thermal event. The giant Muruntau Au deposit formed in the low-strain hornfels rocks at ca. 288 Ma at the intersection of one of the east-west splays, the Sangruntau-Tamdytau shear zone, with a NE-trending regional fault zone, the Muruntau-Daugyztau fault, which likely formed as a cross fault during the onset of left-lateral translation on the regional splays. Interaction between the two faults opened a large dilational zone along a plunging anticlinorium fold nose that served as a major site for hydrothermal fluid focusing. The Au ores are dominantly present as a series of moderately to steeply dipping quartz ± K-feldspar stockwork systems surrounding uncommon central veins and with widespread lower Au-grade metasomatites (i.e., disseminated ores). Pervasive alteration is biotite-K-feldspar, although locally albitization is dominant. Sulfides are mainly arsenopyrite, pyrite, and lesser pyrrhotite, and scheelite may be present both in preore ductile veins and in the more brittle auriferous stockwork systems. The low-salinity, aqueous-carbonic ore-forming fluids probably deposited the bulk of the ore at 400 ° ± 50 ° C and 6-to 10-km paleodepth. The genesis of the deposit remains controversial with metamorphic, thermal aureole gold (TAG), and models related to mantle upwelling all having been suggested in recent years. More importantly, the question as to why there was such a focusing of so much Au and fluid into this one location, forming an ore system an order of magnitude larger than other giant Au deposits in metamorphic terranes, remains unresolved.