The Goiás Archean Block (GAB) in central Brazil is an important gold district that hosts several world-class orogenic gold deposits. A better comprehension of the crustal, tectono-magmatic, and metallogenic settings of the GAB is essential to accurately define its geological evolution, evaluate Archean crustal growth models, and target gold deposits. We present an overview of gold systems, regional whole-rock Sm-Nd analyses that have been used to constrain the geological evolution of the GAB, and augment this with new in situ zircon U-Pb and Hf-O isotope data. The orogenic gold deposits show variable host rocks, structural settings, hydrothermal alteration, and ore mineralogy, but they represent epigenetic deposits formed during the same regional hydrothermal event. The overprinting of metamorphic assemblages by ore mineralogy suggests the hydrothermal event is post-peak metamorphism. The metamorphic grade of the host rocks is predominantly greenschist, locally reaching amphibolite facies. Isotope-time trends support a Mesoarchean origin of the GAB, with ocean opening at 3000–2900 Ma, and reworking at 2800–2700 Ma. Crustal growth was dominated by subduction processes via in situ magmatic additions along lithospheric discontinuities and craton margins. This promoted a crustal architecture composed of young, juvenile intra-cratonic terranes and old, long-lived reworked crustal margins. This framework provided pathways for magmatism and fluids that drove the gold endowment of the GAB.