The tectonic configuration and evolution of southern Appalachian orogenic episodes are constrained, to a large extent, by knowledge of the timing and environment of pre- or syn-orogenic sediment deposition along with their subsequent thermal and deformational histories. The orogenic events that gave rise to regional folding and Barrovian metamorphism of the Western Blue Ridge (WBR) terrane are a classic example. We present new U-Pb and 40Ar-39Ar results bearing on the timing of magmatism and subsequent metamorphism of the Marble Hill Hornblende Schist (MHHS) of the WBR (southeastern USA). The schist is a key marker unit in the Murphy synclinorium, a central structure in the tectonic configuration of the WBR. The MMHS originated as basaltic volcanics overlying the Murphy Marble at the base of the Mineral Bluff Group. Ocean island basalt geochemistry and a zircon U-Pb age of ca. 437 Ma for the MHHS is consistent with plume-related volcanism in a Silurian remnant ocean basin of the Iapetus Ocean. Hornblende 40Ar-39Ar and rutile U-Pb ages for the MHHS are ca. 380−340 Ma and ca. 320 Ma, respectively, and record subsequent amphibolite facies metamorphism during Devonian Acadian orogeny and the deformation through regional folding and thrusting during the Carboniferous Alleghanian orogeny. The new age constraints for the MHHS require that “isograds” mapped in the region of the Murphy Belt are actually polymetamorphic mineral distributions that developed at least in part through post-Silurian tectonic events.