Arsenic and fluoride in groundwater from Quaternary loess deposits in Argentina pose major health concerns. Common sources for arsenic and fluoride have been suggested but the processes of mobilization are disputed, and distributions in groundwater are largely unresolved at a sample density >1/50 km2. At Los Pereyras in Tucumán Province, northern Argentina, we have evaluated distributions and hydrochemical associations of arsenic and fluoride with a sample density of 0.75 per km2 over an area of 75 km2, to a depth of 230 m. Groundwater in the loess is oxic and alkaline. Fluoride is restricted to the upper 20 m of the Quaternary loess, where it reaches 8.3 mg/l. Arsenic has a vertical layering consistent with that of fluoride, ranging from 20 to 760 μg/l in the upper 20 m and 58–163 μg/l below this. There are two sources of arsenic, one unrelated to the fluoride source. Positive correlations between arsenic and fluoride with pH, but not with alkalinity, support desorption from iron oxyhydroxides as the likely mechanism of release to groundwater for arsenic and fluoride, rather than the weathering of silicate minerals. Stratigraphic and/or palaeohydrological controls may explain the observed depth distributions within the loess aquifer.