Greenstone belts preserved in the West African Craton (2300–2070 Ma) provide key information for understanding the petrogenetic processes and geodynamic setting for juvenile crust formation during a nascent Paleoproterozoic plate tectonic regime. New geochemical and isotopic data are presented for the magmatic suites exposed in Sefwi Greenstone Belt, SW Ghana. We define five distinct plutonic suites, with extrusive equivalents, including: 1) two generations of high SiO2, Na2O-rich tonalite-trondhjemite-granodiorite (TTG) granitoids; 2) calc-alkaline, LILE-enriched diorites; 3) tholeiitic pyroxenite, gabbro and layered mafic intrusives; 4) high-K quartz monzonites; and, 5) incompatible element-rich, two-mica granites and muscovite leucogranites. Trace element patterns of most magmatic suites display negative Nb-Ta, P and Ti anomalies and weakly positive Pb anomalies, suggesting magma genesis in a subduction setting with minor crustal contamination/assimilation. Complementary zircon U-Pb and Lu-Hf data indicate contemporaneous emplacement of diorites (εHf(t) = +2.5 to +5.4) and low-HREE TTGs (εHf(t) = +4.3 to +7.6) between ca. 2159 and 2153 Ma, derived from contrasting sources, namely the partial melting of the metasomatised mantle wedge and high-pressure partial melting of low-K mafic sources, respectively. High-HREE TTGs are attributed to the shallow, partial melting of mafic material. The emplacement of high-K quartz monzonites (εHf(t) = +2.5 to +5.2) at ca. 2135 Ma reveals mixing of mantle-derived magmas and remelting of existing TTGs in the crustal pile. Consistently positive εHf(t) values indicate predominantly radiogenic, though heterogeneous, magma sources during crustal growth, derived from precursory material extracted from the depleted mantle and an older crustal component with a minimum age of 2650 Ma. Magmatogenesis of two-mica granites and leucogranites (ca. 2092 and 2081 Ma) is interpreted to be the product of crustal anatexis during an oceanic arc-arc collisional event, with a proposed suture parallel to the NW margin of the Sefwi Belt. We hypothesise that the formation and accretion of the West African Craton reflects the rapid amalgamation of individual oceanic arc terranes, providing potential insight into the transitional plate tectonic regime that may have characterised the Earth between 3000 and 2000 Ma.