The Juruena Mineral Province is an emerging world-class mineral province in the southern Amazonian Craton, due to numerous Au-Cu and base metal deposits, such as the Raimunda deposit, related to Novo Mundo 2.03–1.98 Ga I-type calc-alkaline granites. Its hydrothermal alteration zones comprise Na-metasomatism, microclinization, propylitic and sericitic alteration, silicification, a sulfide stage, and late carbonate alteration. The disseminated mineralization, associated with the sulfide stage, the main mineralization stage, is represented by gold inclusions and fracture-filling grains in pyrite, chalcopyrite, and Cu-Bi sulfides. Chlorite geothermometer and fluid inclusion data indicate temperature conditions of 325–380 °C for the mineralization. The coexistence of high-temperature aqueous and aqueous-carbonic fluid inclusions, based on a microthermometric study of fluid inclusions, reveals a mixing of medium-saline hot fluids with cooler and low-saline fluid. The δ18Ofluid (3.11–7.86‰) and δ34Spy data (−1.4–0.1‰) are coherent to the magmatic origin of the mineralizing fluid. Gold was initially transported as chlorine complexes in a hot, high-salinity, acidic, and oxidized fluid from the magma chamber, and later as H2S− complexes. The chemical-physical instability during fluid ascent is interpreted as a triggering factor for ore precipitation. The results offer valuable insights into the genesis of porphyry–Au deposits and their implications for prospecting in the Amazonian Craton.