Arsenic contamination of groundwater continues to threaten the health of millions of people in southeast Asia. The oxidation of organic carbon, coupled to the reductive dissolution of arsenic-bearing iron oxides, is thought to control the release of sediment-bound arsenic into groundwater. However, the cause of the high spatial variability in groundwater arsenic concentrations—which can range from 5 to 500 μg l−1 within distances of a few kilometres—has been uncertain. Here, we combine measurements of sediment age, organic-matter reactivity and water chemistry at four locations along a cross-section of the arsenic-contaminated Red River floodplain in Vietnam to determine the origin of variations in groundwater arsenic concentrations. The burial age of the aquifer sediments, determined using optical stimulated luminescence, ranged from 460 years near the course of the present-day river to 5,900 years at the margin of the floodplain. The groundwater arsenic content and the reactivity of sedimentary organic carbon, determined using radiotracer measurements of the rate of methanogenesis, declined with sediment age. The sedimentary pools of both iron and arsenic also declined with the burial age of the sediments. We suggest that the age of aquifer sediments is a key determinant of groundwater arsenic concentrations.