The Cobalt Embayment is a large (~60,000 km2), irregular domain of Paleoproterozoic (2.5–2.2 Ga) siliciclastic sedimentary rocks (i.e., the Huronian Supergroup) that unconformably overlies Archean basement rocks of the Abitibi greenstone belt. The Nipissing Diabase, regionally distributed complex of mafic sills and dikes intruded the Huronian sedimentary rocks ca. 2.2 Ga. The sedimentary rocks were subsequently affected by subgreenschist facies metamorphism and by a regionally distributed K and Na metasomatic events, at ca. 1.7 Ga, related to the Penokean orogeny. Although best known for the economically important Ag-Co veins of the Cobalt mining camp, the Cobalt Embayment also hosts numerous other hydrothermal, base and precious metal-mineralized calcite-quartz vein systems. The lead isotope compositions of pyrite and chalcopyrite from nine widely separated polymetallic vein systems yield a Pb-Pb errorchron age of 2236 ± 180 Ma (n = 24). In contrast, the Pb isotope compositions of late-stage galena (n = 11) from six regionally distributed vein systems yield a Pb-Pb secondary isochron age of ca. 1675 Ma. These Pb isotope data for the mineralized vein systems demonstrate the occurrence of at least two major episodes of hydrothermal fluid activity throughout the Cobalt Embayment, ca. 2220 Ma and ca. 1700 Ma, indicate that the emplacement of the Nipissing Diabase was the most likely driver of regional hydrothermal fluid circulation at ca. 2200 Ma, and provide supporting evidence for the basin-wide extent of the regional K and Na metasomatic event at ca. 1700 Ma, most likely related to the waning stages of the Penokean orogeny.