We present an apatite fission-track (AFT) study of five plutonic rocks and seven metamorphic rocks across 310 km of the Yukon–Tanana Upland in east-central Alaska. Samples yielding ~40 Ma AFT ages and mean confined track lengths > 14 µm with low standard deviations cooled rapidly from >120°C to <50°C during a 3–5 Ma period, beginning at about 40 Ma. Data from samples yielding AFT ages >40 Ma suggest partial annealing and, therefore, lower maximum temperatures (~90–105°C). A few samples with single-grain ages of ~20 Ma apparently remained above ~50°C after initial cooling. Although the present geothermal gradient in the western Yukon–Tanana Upland is ~32°C/km, it could have been as high as 45°C/km during a widespread Eocene intraplate magmatic episode. Prior to rapid exhumation, samples with ~40 Ma AFT ages were >3.8–2.7 km deep and samples with >50 Ma AFT ages were >3.3–2.0 km deep. We calculate a 440–320 m/Ma minimum rate for exhumation of all samples during rapid cooling. Our AFT data, and data from rocks north of Fairbanks and from the Eielson deep test hole, indicate up to 3 km of post-40 Ma vertical displacement along known and inferred northeast-trending high-angle faults. The predominance of 40–50 Ma AFT ages throughout the Yukon–Tanana Upland indicates that, prior to the post-40 Ma relative uplift along some northeast-trending faults, rapid regional cooling and exhumation closely followed the Eocene extensional magmatism. We propose that Eocene magmatism and exhumation were somehow related to plate movements that produced regional-scale oroclinal rotation, northward translation of outboard terranes, major dextral strike-slip faulting, and subduction of an oceanic spreading ridge along the southern margin of Alaska.