The Mantoverde iron oxide copper-gold (IOCG) district, northern Chile, is known for its Cu production from supergene ores. Recently, exploration outlined an additional hypogene ore resource of 440 Mt with 0.56 percent Cu, and 0.12 g/t Au. The hypogene sulfide mineralization occurs mainly as chalcopyrite and pyrite, typically in specularite or magnetite-cemented breccias and associated stockworks. The host rocks underwent variably intense K feldspar alteration, chloritization, sericitization, silicification, and/or carbonatization. A district scale Na(-Ca) alteration is absent. The IOCG mineralization in the district shows a strong tectonic control by northwest- to north-northwest–trending brittle structures. Large Cu sulfide-rich veins or Cu sulfide-cemented breccias are absent. Therefore, head grades of 4 percent Cu are an exception. There is a positive correlation between Cu and Au grades. Gold is probably contained mostly in chalcopyrite and pyrite. Elevated concentrations of light rare-earth elements (LREE) occur locally but are attributed to redistribution of LREE within the deposits rather than to derivation from external sources. The Cu-Au ores in the Mantoverde district are low in U and have relatively low contents in heavy metals that are potentially hazardous to the environment, such as As (avg 14 ppm), Hg (<5 ppm), or Cd (<0.2 ppm). The sulfur isotope ratios of chalcopyrite from the IOCG deposits lie between −5.6 and 8.9 per mil δ34SVCDT. They show systematic variations within the district, which are interpreted to reflect relative distance to inferred fluid conduits and the level of deposition within the hydrothermal system. Most initial 87Sr/86Sr values of altered volcanic rocks and hydrothermal calcite from the Mantoverde district are between 0.7031 and 0.7060 and are similar to those of the igneous rocks of the region. Lead isotope ratios of chalcopyrite are consistent with Pb (and by inference Cu) derived from Early Cretaceous magmatism. The sulfur, strontium, and lead isotope data of chalcopyrite, calcite gangue, or altered host rocks, respectively, are compatible with a genetic model that involves cooling of metal and sulfur-bearing magmatic-hydrothermal fluids that mix with meteoric waters or seawater at relatively shallow crustal levels. An additional exotic sulfur input is likely, though not required, for the copper mineralization. Apart from the IOCG deposits, there are a number of smaller magnetite(-apatite) bodies in the district. These are geologically similar to the Cu-Au–bearing magnetite bodies, but are related to splays of the north-south–trending Atacama fault zone and differ in alteration and texture.