We present the results of a Trans‐Alaska Crustal Transect (TACT) investigation of the upper 2–5 km of the eastern Alaska Range in the vicinity of the Denali fault based on seismic reflection/refraction data, laboratory measurements of rock velocities, and structural mapping. The Denali fault is a major dextral slip structure mappable for more than 2000 km separating the Wrangellia and adjacent terranes to the south from the Yukon‐Tanana and adjacent terranes to the north. Geologic mapping suggests over 400 km of dextral slip has occurred on the fault, yet within the upper 1.5 km of the crust along the TACT corridor, basement rocks juxtaposed along the Denali fault reveal no significant seismic velocity differences, although the fault zone itself is associated with a minor lowering of velocity. The lack of seismic velocity contrast adjacent to the fault is in agreement with laboratory measurements of elastic wave velocities of samples from terranes bordering the fault. Laboratory measurements of elastic wave velocities of the metasedimentary mica‐quartz schists comprising the Yukon‐Tanana basement are highly anisotropic because of preferred orientation of mica and predict significant variations in velocity accompanying variations in foliation dip. Although other interpretations are possible, the northward shallowing of foliation dip of basement rocks in the Yukon‐Tanana terrane combined with the strong anisotropy associated with these highly foliated rocks can explain an observed northward increase in seismic velocity within this terrane. Seismic reflections from basement rocks within the Yukon‐Tanana terrane may originate from variations in anisotropy with depth and/or changes in composition reflecting different proportions of sandstone and shale in the protolith.