The Mesoarchean (ca. 3075 Ma) Ivisaartoq greenstone belt in southern West Greenland includes variably deformed and metamorphosed pillow basalts, ultramafic flows (picrites), serpentinized ultramafic rocks, gabbros, sulphide-rich siliceous layers, and minor siliciclastic sedimentary rocks. Primary magmatic features such as concentric cooling-cracks and drainage cavities in pillows, volcanic breccia, ocelli interpreted as liquid immiscibility textures in pillows and gabbros, magmatic layering in gabbros, and clinopyroxene cumulates in ultramafic flows are well preserved in low-strain domains. The belt underwent at least two stages of calc-silicate metasomatic alteration and polyphase deformation between 2963 and 3075 Ma. The stage I metasomatic assemblage is composed predominantly of epidote (now mostly diopside) + quartz + plagioclase ± hornblende ± scapolite, and occurs mainly in pillow cores, pillow interstitials, and along pillow basalt-gabbro contacts. The origin of this metasomatic assemblage is attributed to seafloor hydrothermal alteration. On the basis of the common presence of epidote inclusions in diopside and the local occurrence of epidote-rich aggregates, the stage I metasomatic assemblage is interpreted as relict epidosite. The stage II metasomatic assemblage occurs as concordant discontinuous layered calc-silicate bodies to discordant calc-silicate veins commonly associated with shear zones. The stage II metasomatic assemblage consists mainly of diopside + garnet + amphibole + plagioclase + quartz ± vesuvianite ± scapolite ± epidote ± titanite ± calcite ± scheelite. Given that the second stage of metasomatism is closely associated with shear zones and replaced rocks with an early metamorphic fabric, its origin is attributed to regional dynamothermal metamorphism. The least altered pillow basalts, picrites, gabbros, and diorites are characterized by LREE-enriched, near-flat HREE, and HFSE (especially Nb)-depleted trace element patterns, indicating a subduction zone geochemical signature. Ultramafic pillows and cumulates display large positive initial e_Nd values of + 1.3 to + 5.0, consistent with a strongly depleted mantle source. Given the geological similarities between the Ivisaartoq greenstone belt and Phanerozoic forearc ophiolites, we suggest that the Ivisaartoq greenstone belt represents Mesoarchean supra-subduction zone oceanic crust.