The Yukon–Alaska Highway corridor in southern Yukon is subject to geohazards ranging from landslides to floods and earthquakes on faults in the St. Elias Mountains and Shakwak Valley. Here we discuss the late Holocene seismic history of the Denali fault, located at the eastern front of the St. Elias Mountains and one of only a few known seismically active terrestrial faults in Canada. Holocene faulting is indicated by scarps and mounds on late Pleistocene drift and by tectonically deformed Pleistocene and Holocene sediments. Previous work on trenches excavated against the fault scarp near the Duke River reveals paleoseismic sediment disturbance dated to ∼300–1,200, 1,200–1,900, and 3,000 years ago. Re-excavation of the trenches indicates a fourth event dated to 6,000 years ago. The trenches are interpreted to show a negative flower structure produced by extension of sediments by dextral strike-slip fault movement. Nearby Crescent Lake is ponded against the fault scarp. Sediment cores reveal four abrupt sediment and diatom changes reflecting seismic shaking at ∼1,200–1,900, 1,900–5,900, 5,900–6,200, and 6,500–6,800 years ago. At the Duke River, the fault offsets sediments, including two White River tephra layers (∼1,900 and 1,200 years old). Late Pleistocene outwash gravel and overlying Holocene aeolian sediments show in cross section a positive flower structure indicative of post-glacial contraction of the sediments by dextral strike-slip movement. Based on the number of events reflecting ∼M6, we estimate the average recurrence of large earthquakes on the Yukon part of the Denali fault to be about 1,300 years in the past 6,500–6,800 years.