Gold- and iron sulfide-bearing deposits of the southeastern United States have distinctive mineralogical and geochemical features that provide a basis for constructing models of ore genesis for exploration and assessment of gold resources. The largest (historic) deposits, in approximate million ounces of gold (Moz Au), include those in the Haile (~ 4.2 Moz Au), Ridgeway (~1.5 Moz Au), Brewer (~0.25 Moz Au), and Barite Hill (0.6 Moz Au) mines. Host rocks are Late Proterozoic to early Paleozoic (~553 million years old) metaigneous and metasedimentary rocks of the Carolina Slate Belt that share a geologic affinity with the classic Avalonian tectonic zone. The inferred syngenetic and epithermal-subvolcanic quartz-porphyry settings occur stratigraphically between sequences of metavolcanic rocks of the Persimmon Fork and Uwharrie Formations and overlying volcanic and epiclastic rocks of the Tillery and Richtex Formations (and regional equivalents). The Carolina Slate Belt is highly prospective for many types of gold ore hosted within quartz-sericite-pyrite altered volcanic rocks, juvenile metasedimentary rocks, and in associated shear zones. For example, sheared and deformed auriferous volcanogenic massive sulfide deposits at Barite Hill, South Carolina, and in the Gold Hill trend, North Carolina, are hosted primarily by laminated mudstone and felsic volcanic to volcaniclastic rocks. The high-sulfidation epithermal style of gold mineralization at Brewer and low-sulfidation gold ores of the Champion pit at Haile occur in breccias associated with subvolcanic quartz porphyry and within crystal-rich tuffs, ash flows, and subvolcanic rhyolite. The Ridgeway and Haile deposits are primarily epithermal replacements and feeder zones within (now) metamorphosed crystal-rich tuffs, volcaniclastic sediments, and siltstones originally deposited in a marine volcanic-arc basinal setting. Recent discoveries in the region include (1) extensions of known deposits, such as at Haile where drilling has identified an extensive gold-rich feeder system; and (2) newly discovered prospects like the porphyry-style gold-copper-molybdenum occurrence reported at Deep River, N.C. Gold ores at Ridgeway and Haile represent the low-sulfidation, disseminated, shallow subaqueous tuffaceous equivalents of intrusion-related high-sulfidation ores such as those at Brewer. Haile also has mineralogical features that support a stockwork disseminated model of pyrite-gold-sericite mineralization in which a significant amount of ore was deposited in sediments at or near the surface. The potential is high for gold-rich ore at depth in the funnel-shaped feeder zones that likely underlie such surface variants of high sulfidation–low sulfidation epithermal systems and for new discoveries of similar deposits in areas undercover. Exploration strategies for large-scale gold-mineralizing systems applied to rocks of the Carolina Slate Belt, and by extension, the Carolinian-Avalonian tectonic zone of North America, benefit from applying subvolcanic and basinal epithermal models for gold mineralization.