Geogenic groundwater arsenic (As) contamination is pervasive in many aquifers in south and southeast Asia. It is feared that recent increases in groundwater abstractions could induce the migration of high-As groundwaters into previously As-safe aquifers. Here we study an As-contaminated aquifer in Van Phuc, Vietnam, located ~10 km southeast of Hanoi on the banks of the Red River, which is affected by large-scale groundwater abstraction. We used numerical model simulations to integrate the groundwater flow and biogeochemical reaction processes at the aquifer scale, constrained by detailed hydraulic, environmental tracer, hydrochemical and mineralogical data. Our simulations provide a mechanistic reconstruction of the anthropogenically induced spatiotemporal variations in groundwater flow and biogeochemical dynamics and determine the evolution of the migration rate and mass balance of As over several decades. We found that the riverbed–aquifer interface constitutes a biogeochemical reaction hotspot that acts as the main source of elevated As concentrations. We show that a sustained As release relies on regular replenishment of river muds rich in labile organic matter and reactive iron oxides and that pumping-induced groundwater flow may facilitate As migration over distances of several kilometres into adjacent aquifers.