The Hurricane Fault is a ~250-km-long, west-dipping normal fault located along the transition between the Colorado Plateau and Basin and Range tectonic provinces in the western U.S. Extensive evidence of fluid-fault interaction, including calcite mineralization and veining, occur in the footwall damage zone. Calcite vein carbon (δ<sub>13</sub>C<sub>VPDB</sub>) and oxygen (δ<sub>18</sub>O<sub>VPDB</sub>) stable isotope ratios range from −4.5 to 3.8 ‰ and −22.1 to −1.1 ‰, respectively. Fluid inclusion microthermometry constrain paleofluid temperatures and salinities from 45–160 °C and 1.4–11.0 wt % as NaCl, respectively. These data identify mixing between two primary fluid sources including infiltrating meteoric groundwater (70 ± 10 °C, ~1.5 wt % NaCl, δ<sub>18</sub>O<sub>SMOW</sub> ~−10 ‰) and sedimentary brine (100 ± 25 °C, ~11 wt % NaCl, δ<sub>18</sub>O<sub>SMOW</sub> ~5 ‰). Interpreted carbon sources include crustal- or magmatic-derived CO<sub>2</sub>, carbonate bedrock, and hydrocarbons. U-Th dates from 5 calcite vein samples indicates punctuated fluid-flow and fracture healing at 539 ± 10.8, 287.9 ± 5.8, 86.2 ± 1.7, and 86.0 ± 0.2 ka in the upper 300 m of the crust. Collectively, the data imply that the Hurricane Fault imparts a strong influence on regional flow of crustal fluids, and that the formation of veins in the shallow parts of the fault damage zone has important implications for the evolution of fault strength and permeability.