New U–Pb ID-TIMS geochronological and whole-rock geochemical data from the Hurry Inlet Plutonic Terrane in Liverpool Land provide evidence of a Late Ordovician to Silurian magmatic arc in the East Greenland Caledonides. These voluminous granitoid rocks range from meladiorite to monzonite and granite, they are alkali-calcic to calc-alkaline and magnesian, and have characteristic arc granitoid trace element signatures. Zircon data give ages of 446 ± 2 and 438 ± 4 Ma for two phases of the Hurry Inlet Composite Pluton, 426 ± 1 Ma for a meladioritic xenolith in the anatectic Triaselv granite, and 424 ± 1 Ma for the Hodal-Storefjord Pluton. The Late Ordovician plutons can be correlated with similar plutons in the uppermost nappes of the Scandinavian Caledonides, likely representing the northern branch of magmatic arcs formed on the Laurentian margin. Magmatism appears to have continued sporadically until about 425 Ma when a major, short-lived, magmatic event formed the bulk of the batholith on Liverpool Land. This activity was likely mantle-driven and can be correlated with the Newer Granites in Scotland, for which a slab break-off mechanism has been proposed. The increased heat flow from this process can also explain the generation of the crustally derived, syntectonic, two-mica granites, which are the areally most important Caledonian suite in East Greenland.