The Liverpool Land – Canning Land region in East Greenland is the central-most basement high in the northeast Atlantic Caledonides. It contains a variety of rocks derived from the whole section of the Caledonian crust, permitting correlations and comparisons of tectonomagmatic events at all crustal levels. Here, we present U–Pb thermal ionization mass spectrometry (TIMS) data combined with field studies suggesting that the region can be divided into distinct tectonostratigraphic domains: (1) The Southern Liverpool Land eclogite terrane with garnet-peridotite and eclogite lenses, the product of a polyorogenic history with a latest-Paleoproterozic and Mesoproterozoic origin, eclogitization at 398 Ma and migmatization at 387 Ma. (2) The migmatitic Mariager Fjord Dome in central Liverpool Land with gneisses that formed leucosome at 409 Ma. Both areas are separated by high-strain zones from (3) the overlying Hurry Inlet plutonic terrane, which consists of metasedimentary rocks first intruded by granodiorite to granite at ca. 440–430 Ma, and, after local deformation, by a major 426–424 Ma granitic to monzonitic suite. (4) Structurally higher, and probably above another high-strain zone, low-grade Neoproterozoic to Cambrian sediments are intruded, by syn-contractional 427 Ma leucogranite. All these units are unconformably overlain by Devonian and younger deposits. Collectively our data document a distinct variation in time for Caledonian magmatism and metamorphism in the various tectonostratigraphic domains, implying that the diverse terranes were juxtaposed after magmatism, and that the gneiss domes of Liverpool Land have a different origin than other nappes of the East Greenland Caledonides.