Pollution of groundwater with natural (geogenic) arsenic occurs on an enormous, world-wide scale, and causes wide-spread, serious health risks for an estimated more than hundred million people who depend on the use of shallow aquifers for drinking and irrigation water. A literature review of key studies on arsenic concentration levels yields that Holocene fluvial and deltaic flood basins are the hotspots of arsenic pollution, and that the dominant geomorphological setting of the arsenic-polluted areas consists of shallow-depth meandering-river deposits with sand-prone fluvial point-bar deposits surrounded by clay-filled (clay plug) abandoned meander bends (oxbow lakes). Analysis of the lithofacies distribution and related permeability contrasts of the geomorphological elements in two cored wells in a point bar and adjacent clay plug along the Ganges River, in combination with data of arsenic concentrations and organic matter content reveals that the low-permeable clay-plug deposits have a high organic matter content and the adjacent permeable point-bar sands show high but spatially very variable arsenic concentrations. On the basis of the geomorphological juxtaposition, the analysis of fluvial depositional processes and lithofacies characteristics, inherent permeability distribution and the omnipresence of the two geomorphological elements in Holocene flood basins around the world, a generic model is presented for the wide-spread arsenic occurrence. The anoxic deeper part (hypolimnion) of the oxbow lake, and the clay plugs are identified as the loci of reactive organic carbon and microbial respiration in an anoxic environment that triggers the reductive dissolution of iron oxy-hydroxides and the release of arsenic on the scale of entire fluvial floodplains and deltaic basins. The adjacent permeable point-bar sands are identified as the effective trap for the dissolved arsenic, and the internal permeability heterogeneity is the cause for aquifer compartmentalization, with large arsenic concentration differences between neighboring compartments.