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The chronological repartition of mineral deposits in Mexico and the southern USA coincides with the distribution of the three main volcanic pulses of the Sierra Madre Occidental. These pulses are Eocene to early Miocene in age, suggesting that a broad migration occurred from northwest to southeast, where the last ignimbrite flare-up occurred. The most fertile event occurred from 36 to 28 Ma and produced all of the largest Ag-Au mining districts. The Placer de Guadalupe Au-U district contain a unique association of metals with high variations in their U/Au ratios that are not common worldwide. The uraninite population dated by Wells (1930) yielded an age of ca. 36 Ma, which is comparable to that of the volcanic intrusions and dykes dated in the district (yielding ages of ca. 36 Ma). Altered uraninite cemented by gold sheets provide an age of 21 Ma, which is interpreted to be the age of the gold epithermal event. Studies of fluid inclusions in the quartz and calcite cements formed in the gold event indicate the presence of immiscible magmatic brines and CO 2 . Homogenization temperatures by halite melting range from 268 °C to 305 °C and 266.6 °C to 283 °C, with salinities ranging from 35.9 to 38.9 and 36.0 to 37.5 wt% eq NaCl, in the quartz and calcite stages, respectively. C-O isotopic compositions of U and Au calcite cements suggest a trend of low-temperature alteration caused by hydrothermal fluids. These C-O isotopes suggest that during the gold event, water/rock interaction processes occurred between magmatic fluids and the carbonate host-rock. REE enrichment in the U calcite cement suggests that La-Ce enriched carbonatite volcanic formations participated in the mineralizing process. The U mineralization event was controlled by (1) a metal and heat source (in this case, late Eocene volcanism and, in particular, a carbonatite volcanic event); (2) an efficient transport mechanism for the large-scale input of meteoric water, which was channeled, heated and U-enriched into reactivated crustal Eocene faults from a deep U source to a shallow sedimentary chemical trap; (3) an effective trap, which is represented in this study by the presence of an organic matter-rich sedimentary formation. The gold mineralization event was characterized by the Miocene extensional peak coupled with asthenospheric upwelling, which facilitated the melting/metamorphism of the lower crust and the expulsion and transport of large amounts of CO 2 -bearing fluids to a shallow crustal level through the reactivated crustal Laramide thrust faults. The fluids’ interactions with the entire stratigraphic column, from the Grenvillian to the Late Triassic basement, favored the leaching of gold and the enrichment of CO 2 -bearing fluids. Gold deposition appears to be related to boiling but was ultimately favored by water-rock interaction with U mineralization and the Upper Plomosas shale. Study of the Au-U Placer de Guadalupe deposit reveals evidence of a new Miocene metallogenic event in central and northern Mexico. Its genetic relationship with the Basin and Range (BnR) and Rio Gande Rift (RGR) in USA and its transition from post-orogenic to Miocene intraplate extension in Mexico provides a new perspective regarding the exploration of Miocene gold epithermal deposits in northern Mexico and the southern USA. [ABSTRACT FROM AUTHOR]