The Tres Marias Zn-Pb-(Ge) deposit in Chihuahua, northern Mexico, is hosted by mid-Cretaceous carbonate rocks. Sulfide ore occurs in a carbonate solution collapse breccia and has been partially altered to zinc silicates and oxides. We have used Rb-Sr sphalerite geochronology and Pb isotope systematics to constrain the age and genesis of the sulfide mineralization. An Rb-Sr sphalerite age of 28.8 ± 1.7 Ma was obtained from a quantitative, two-component paleomixing model. This age coincides with widespread volcanism in the region and is associated with a marked change from a compressional to an extensional tectonic regime. Furthermore, the Pb isotope compositions of galena, sphalerite, and late-stage hydrothermal calcite of the Tres Marias deposit overlap with values for coeval magmatic-hydrothermal, high-temperature Zn-Pb deposits of northern Chihuahua.We conclude that the formation of the Tres Marias deposit is related to magmatism and the onset of Basin and Range extensional tectonics, even though no direct spatial link between magmatic rocks and the mineralization is apparent.