The high strain zone separating infracrustal ortho- and paragneisses from supracrustal cover rocks in the East Greenland Caledonides has been interpreted variously as (1) a combined Grenvillian and Caledonian thrust, (2) a Vendian extensional shear zone reactivated as a Caledonian thrust, (3) a Caledonian extensional detachment reactivated as a late Caledonian thrust or (4) a late Caledonian extensional detachment. In this study we present new kinematic and geochronological data (U–Pb and 40Ar/39Ar) from a well-studied segment of the high strain zone in Kejser Franz Joseph Fjord, demonstrating top-to-the-east, normal-sense displacement. Syntectonic peraluminous granites in the infrastructure are interpreted to have formed by decompressional anatexis (c. 430–425 Ma) and were later deformed to ultramylonites, cataclasites and psudotachylites along the high strain zone. Extension related fabrics overprint earlier and are synchronous with contractional top-to-the-NW thrust faults and associated structures. Muscovite records progressively younger 40Ar/39Ar cooling ages (from 408 to 388 Ma) downward in the extensional footwall, whereas feldspar from the mylonites yield a closure age of 349 Ma. Foreland-directed shortening in the East Greenland Caledonides lasted until at least Early Devonian times, while orogenic extensional collapse initiated along the zone of high strain during the Late Silurian in an overall collisional setting. Upper crustal thinning continued well into the Devonian along increasingly more narrow and brittle extensional faults.