The Santa María and Antares Zn-Pb(-Ag) skarn deposits in the Velardeña Mining District are located in central–NW Mexico. They lie 470 m apart along the contact between Oligocene felsic intrusions and Cretaceous limestones, and were developed during prograde, retrograde, post-ore (Santa María), and late stages. Firstly, the prograde stage was formed by fluids at ~ 600 °C and 15 wt% NaCl equiv., and consists of garnet + wollastonite ± clinopyroxene and biotite ± K-feldspar assemblages. Secondly, the retrograde/ore stage was formed by fluids at 300–500 °C with salinities of 20–30 wt% CaCl2 (Santa María) and > 40 wt% NaCl equiv. (Antares). It comprises assemblages of chlorite, amphibole, epidote, calcite, scapolite, quartz, sericite, adularia, fluorite, and muscovite associated with sphalerite, pyrite, galena, pyrrhotite, arsenopyrite, chalcopyrite, and Pb-Bi-Sb sulfosalts. Thirdly, the post-ore stage was formed by fluids at ~ 400 °C and 20–30 wt.% CaCl2 and comprises poorly mineralized calcite veins. Fourthly, the late stage was formed by fluids at < 300 °C and 20–30 wt.% CaCl2 (Santa María) and ~ 15 wt% NaCl equiv. (Antares), and crystallized tetrahedrite-group minerals and pyrite + marcasite. δ18Ofluid between ~ 14‰ and 23‰ at Santa María and between ~ 12‰ and 17‰ at Antares show a less-modified magmatic affinity for mineralizing fluids at Antares; δ13Cfluid between 0‰ and –6‰ register recycling of sedimentary C. Moreover, sulfides with δ34SVCDT between –3‰ and 2‰ reveal a magmatic source for S. Altogether, these data suggest that, at Santa María, magmatic-derived fluids actively interacted with the wall rocks, whereas at Antares the fluid-rock interaction was milder. In both deposits, metal deposition was triggered by the cooling and neutralization of ore-bearing fluids with carbonate rocks. Our 40Ar/39Ar dates for adularia of ca. 37.5 Ma place the deposits within the Eocene–early Miocene metallogenetic epoch of central–NW Mexico, during which other world-class skarn-epithermal systems were emplaced (e.g., Concepción del Oro and Mazapil-Peñasquito).