Sensitive high-resolution ion microprobe (SHRIMP) U–Pb analyses of igneous zircons from the Lake George assemblage in the eastern Yukon–Tanana Upland (Tanacross quadrangle) indicate both Late Devonian (∼370 Ma) and Early Mississippian (∼350 Ma) magmatic pulses. The zircons occur in four textural variants of granitic orthogneiss from a large area of muscovite–biotite augen gneiss. Granitic orthogneiss from the nearby Fiftymile batholith, which straddles the Alaska–Yukon border, yielded a similar range in zircon U–Pb ages, suggesting that both the Fiftymile batholith and the Tanacross orthogneiss body consist of multiple intrusions. We interpret the overall tectonic setting for the Late Devonian and Early Mississippian magmatism as an extending continental margin (broad back-arc region) inboard of a northeast-dipping (present coordinates) subduction zone. New SHRIMP U–Pb ages of inherited zircon cores in the Tanacross orthogneisses and of detrital zircons from quartzite from the Jarvis belt in the Alaska Range (Mount Hayes quadrangle) include major 2.0–1.7 Ga clusters and lesser 2.7–2.3 Ga clusters, with subordinate 3.2, 1.4, and 1.1 Ga clusters in some orthogneiss samples. For the most part, these inherited and core U–Pb ages match those of basement provinces of the western Canadian Shield and indicate widespread potential sources within western Laurentia for most grain populations; these ages also match the detrital zircon reference for the northern North American miogeocline and support a correlation between the two areas.