This paper provides an overview on the genesis of Mesoproterozoic igneous rocks and associated iron oxide ± apatite (IOA) ± rare earth element, iron oxide-copper-gold (IOCG), and iron-rich sedimentary deposits in the St. Francois Mountains terrane of southeast Missouri, USA. The St. Francois Mountains terrane lies along the southeastern margin of Laurentia as part of the eastern granite-rhyolite province. The province formed during two major pulses of igneous activity: (1) an older early Mesoproterozoic (ca. 1.50–1.44 Ga) episode of volcanism and granite plutonism, and (2) a younger middle Mesoproterozoic (ca. 1.33–1.30 Ga) episode of bimodal gabbro and granite plutonism. The volcanic rocks are predominantly high-silica rhyolite pyroclastic flows, volcanogenic breccias, and associated volcanogenic sediments with lesser amounts of basaltic to andesitic volcanic and associated subvolcanic intrusive rocks. The iron oxide deposits are all hosted in the early Mesoproterozoic volcanic and volcaniclastic sequences. Previous studies have characterized the St. Francois Mountains terrane as a classic, A-type within-plate granitic terrane. However, our new whole-rock geochemical data indicate that the felsic volcanic rocks are effusive derivatives from multicomponent source types, having compositional similarities to A-type within-plate granites as well as to S- and I-type granites generated in an arc setting. In addition, the volcanic-hosted IOA and IOCG deposits occur within bimodal volcanic sequences, some of which have volcanic arc geochemical affinities, suggesting an extensional tectonic setting during volcanism prior to emplacement of the ore-forming systems. The Missouri iron orebodies are magmatic-related hydrothermal deposits that, when considered in aggregate, display a vertical zonation from high-temperature, magmatic ± hydrothermal IOA deposits emplaced at moderate depths (~1–2 km), to magnetite-dominant IOA veins and IOCG deposits emplaced at shallow subvolcanic depths. The shallowest parts of these systems include near-surface, iron oxide-only replacement deposits, surficial epithermal sediment-hosted replacement deposits, synsedimentary ironstone deposits, and Mn-rich exhalite deposits. Alteration associated with the IOA and IOCG mineralizing systems of the host volcanic rocks dominantly produced potassic with lesser amounts of calcic- and sodic-rich mineral assemblages. No deposits are known to be hosted in granite, implying that the mineralizing systems were operative during a relatively short, postvolcanic period yet prior to intrusion of the granitoids. Companion studies in this special issue on mineral chemistry, stable isotopes, and iron isotopes suggest that the magnetite within the IOA deposits formed from high-temperature fluids of magmatic or magmatic-hydrothermal origin. However, the data do not discriminate between a magmatic-hydrothermal source fluid exsolved from an Fe-rich immiscible liquid or an Fe-rich silicate magma. Mineral chemical, fluid inclusion, and stable isotope data from these new studies record the effects of metasomatic fluids that interacted with crustal reservoirs such as volcanic rocks or seawater.