To constrain the fluid evolution in the polymetallic Main Stage (MS) veins at Butte, USA, we present microthermometric measurements of fluid inclusions assemblages (FIAs) in co-genetic ore and gangue minerals through the different mineralization stages. Early quartz-hosted FIAs indicate the highest homogenization temperatures (Th, between 290° and 320 °C) with salinity similar to the intermediate density FI of the pre-Main Stage (4 to 6 wt. % NaCl equiv). During the Cu-rich mineralization stage, a drop in salinity to 2 wt.% NaCl equiv. at temperature ~280°C, precedes locally developed phase separation, witnessed by coexisting vapor-rich and liquid-rich FI with similar Th but with higher salinity (2.5 to 7 wt.% NaCl equiv.). Primary FIAs in sphalerite and rhodochrosite from the late mineralization stage indicate fluid temperature (Th~210°C) and salinity (1.7 to 4 wt.% NaCl equiv.) decrease through time, towards the periphery of the district. This study suggests that mixing of a high-temperature fluid with salinity similar to fluids from the pre-Main Stage quartz-pyrite veins with cooler and lower salinity fluids (potentially of meteoric origin) combined with local boiling processes are responsible of the ore precipitation in the MS veins.