Abstract A magmatic and metallogenic framework for the northern Yukon-Tanana terrane of west-central Yukon and eastern Alaska is proposed, which contextualizes syngenetic, intrusion-related, and orogenic styles of mineralization in the region. The framework applies to bedrock gold and base metal enrichments in the Dawson Range, White Gold, Klondike, Sixtymile, and Fortymile districts, which are historically known for their placer gold endowment, but which host few significant bedrock mineral resources. New field and geochronological (U-Pb, 40 Ar/ 39 Ar, 187 Re/ 187 Os) data, along with contributions from exploration companies, provide the key constraints on this framework. Sedimentary exhalative Pb-Zn mineralization and porphyry-style Cu-Au mineralization are associated with Late Devonian to Early Mississippian (365-342 Ma) rocks of the Finlayson assemblage and Simpson Range plutonic suite, respectively—both of which formed in a continental arc built on pre-Late Devonian continental margin sediments (Snowcap assemblage) along the ancient Pacific margin of North America. By the Late Permian, these assemblages had rifted away from North America, and W-dipping subduction of the intervening Slide Mountain Ocean was initiated. Volcanogenic massive sulfide-style Pb-Zn-Cu-(Ag-Au) mineralization formed in subvolcanic to volcanic rocks of the Late Permian (269-253 Ma) Klondike arc assemblage that was built on the Devono-Mississippian arc. Together these assemblages make up the Yukon-Tanana terrane. Gold mineralization formed sparsely with syn- to postmetamorphic Late Permian (253-250 Ma) anatectic melts. Five metallogenic events are recognized that coincide with magmatic episodes superimposed on the Yukon-Tanana terrane: (1) Cu-Au mineralization formed during an Early Jurassic (200-179 Ma) pulse of magmatism and was accompanied by rapid crustal exhumation (e.g., Minto); (2) Au-mineralized breccia complexes, skarns, intermediate-sulfidation epithermal systems, and polymetallic veins are associated with mid-Cretaceous (115-98 Ma) magnetite-series arc magmas in the Dawson Range, whereas age-equivalent Au deposits in the back-arc region to the north are associated with ilmenite-series magmas (e.g., Pogo); (3) variably Cu and Au rich porphyry systems formed within the mid-Cretaceous arc in the early Late Cretaceous (79-72 Ma) (e.g., Casino, Nucleus-Revenue); (4) porphyry Mo and Cu systems and Ag-rich polymetallic veins, carbonate-replacement, and skarn bodies are temporally and spatially associated with NE-trending, sinistral oblique-extensional fault systems in the latest Cretaceous (72-67 Ma); and (5) examples of disseminated U, Cu-Pb-Ag skarn, and Au-Ag epithermal systems are associated with dominantly felsic but locally bimodal Paleocene-Eocene (60-55 Ma) magmatism, emplaced into zones of extension during early activity on the Tintina fault zone. At least two distinct orogenic Au-mineralizing events are recognized. Within a Middle to Late Jurassic hiatus in magmatism, gold mineralization formed at 163 to 155 Ma in brittle-ductile to brittle structures within sinistral fault zones (e.g., White Gold), high-angle reverse faults, and kink folds. A subsequent episode of mid-Cretaceous (96-92 Ma) orogenic gold mineralization formed in structures cutting Paleozoic metamorphic rocks and mid-Cretaceous granitoids (e.g., Moosehorn, Boulevard). Weathering and surficial preservation in this unglaciated region since the Pliocene resulted in economic placer gold endowments in the Klondike, Sixtymile, Fortymile, White Gold, and Dawson Range districts. The framework we describe for the magmatism and metallogeny of west-central Yukon and eastern Alaska provides a testable platform for regional exploration targeting and property-scale exploration in a region with demonstrated mineral potential.