In southwest Yukon, the boundary between the Alexander terrane and Wrangellia corresponds with the Duke River fault. In this paper, we report on observations of the Duke River fault from four localities in southwest Yukon, and provide new constraints on (1) Permian regional metamorphism within the Alexander terrane, (2) Cretaceous ductile deformation along the Duke River fault, and (3) post-Miocene brittle deformation along the fault. Within these areas, the Duke River fault juxtaposes imbricated, pervasively foliated and folded greenschist-facies rocks of the Alexander terrane southwest of the fault against sub-greenschist-facies, less deformed rocks of Wrangellia. Multiple lines of evidence from this region indicate the Alexander terrane has been juxtaposed against Wrangellia along a southwest-dipping thrust fault. 40Ar/39Ar dates from muscovite, which grew during faulting or have been reset by motion along the Duke River fault, range from 79 to 105 Ma, suggesting that ductile movement along the fault is at least as old as Cretaceous (Albian to Cenomanian). This phase of faulting is interpreted as the local expression of Cretaceous shortening, which has been documented along the length and width of the Cordillera. Cretaceous structures along the Duke River fault are overprinted by brittle deformation that affects rocks as young as Miocene (or Pliocene?). The Duke River fault appears to be accommodating present-day transpression through uplift and reactivation of the thrust fault.