Abstract The Freiberg district hosts one of the largest series of epithermal polymetallic vein deposits in Europe. The availability of a systematic collection of historical samples provides an excellent opportunity to study the anatomy of these epithermal systems. Detailed petrographic investigations, geochemical analyses, and fluid inclusion studies were conducted on several vertical profiles within the Freiberg district to decipher mineralogical and geochemical zoning patterns. Six distinctive mineral associations have been recognized within the Freiberg epithermal veins; sphalerite-pyrite-quartz and galena-quartz±carbonate associations are most abundant in the central sector, as well as in the deepest sections of veins on the periphery of the district. A high-grade sphalerite-Ag-sulfides-carbonate association occurs laterally between the central and peripheral sectors and at intermediate depth in veins on the periphery. Shallow and peripheral zones are dominated by an exceptionally Ag-rich Ag-sulfides-quartz association, whereas the shallowest veins locally comprise Ag-poor stibnite-quartz and quartz-carbonate associations. Fluid inclusion assemblages returned low salinities (<6.0 wt % NaCl equiv), and homogenization temperatures successively decrease from ~320°C associated with the proximal and deep sphalerite-pyrite-quartz association, to ~170°C related to the distal and shallow Ag-sulfides-quartz association. The architecture of the Freiberg district is related to the temporal and spatial evolution of magmatic-hydrothermal fluid systems, including boiling and concomitant cooling, as well as CO2 loss. Constraints on the paleodepth indicate that the veins formed between 200 and 1,800 m below the paleowater table. High-grade Ag ore occurs over a vertical interval of at least 500 m and is bracketed by shallower stibnite-quartz and barren quartz, and deeper base metal-sulfide-quartz zones.