Nalunaq is an orogenic, high gold grade deposit situated on the Nanortalik Peninsula, South Greenland. Mineralisation is hosted in shear zone-controlled quartz veins, located in fine- and medium-grained amphibolite. The deposit was the site of Greenland’s only operating metalliferous mine until its closure in 2014, having produced 10.67 t of gold. This study uses a combination of field investigation, petrography and U/Pb zircon and titanite geochronology to define a multi-stage hydrothermal alteration system at Nalunaq. A clinopyroxene-plagioclase-garnet(-sulphide) alteration zone (CPGZ) developed in the Nanortalik Peninsula, close to regional peak metamorphism and prior to gold-quartz vein formation. The ca. 1783–1762-Ma gold-quartz veins are hosted in reactivated shear zones with a hydrothermal alteration halo of biotite-arsenopyrite-sericite-actinolite-pyrrhotite(-chlorite-plagioclase-löllingite-tourmaline-titanite), which is best developed in areas of exceptionally high gold grades. Aplite dykes dated to ca. 1762 Ma cross-cut the gold-quartz veins, providing a minimum age for mineralisation. A hydrothermal calcite-titanite alteration assemblage is dated to ca. 1766 Ma; however, this alteration is highly isolated, and as a result, its field relationships are poorly constrained. The hydrothermal alteration and mineralisation is cut by several generations of ca. 1745-Ma biotite granodiorite accompanied by brittle deformation. A ca. 1745-Ma lower greenschist facies hydrothermal epidote-calcite-zoisite alteration assemblage with numerous accessory minerals forms halos surrounding the late-stage fractures. The contrasting hydrothermal alteration styles at Nalunaq indicate a complex history of exhumation from amphibolite facies conditions to lower greenschist facies conditions in an orogenic belt which resembles modern Phanerozoic orogens.