Recently collected naturally occurring geochemical and isotopic groundwater tracers were combined with historic data from the Pahute Mesa area of the Nevada National Security Site (NNSS), Nevada, USA, to provide insights into long-term regional groundwater flow patterns, mixing and recharge. Pahute Mesa was the site of 85 nuclear detonations between 1965 and 1992, many of them deeply buried devices that introduced radionuclides directly into groundwater. The dataset examined included major ions and field measurements, stable isotopes of hydrogen (δ²H), oxygen (δ¹⁸O), carbon (δ¹³C) and sulfur (δ³⁴S), and radioisotopes of carbon (¹⁴C) and chloride (³⁶Cl). Analysis of the patterns of groundwater ¹⁴C data and the δ²H and δ¹⁸O signatures indicates that groundwater recharge is predominantly of Pleistocene age, except for a few localized areas near major ephemeral drainages. Steep gradients in sulfate (SO₄) and chloride (Cl) define a region near the western edge of the NNSS where high-concentration groundwater flowing south from north of the NNSS merges with dilute groundwater flowing west from eastern Pahute Mesa in a mixing zone that coincides with a groundwater trough associated with major faults. The ³⁶Cl/Cl and δ³⁴S data suggest that the source of the high Cl and SO₄ in the groundwater was a now-dry, pluvial-age playa lake north of the NNSS. Patterns of groundwater flow indicated by the combined data sets show that groundwater is flowing around the northwest margin of the now extinct Timber Mountain Caldera Complex toward regional discharge areas in Oasis Valley.