High groundwater arsenic (As) across the globe has been one of the most well researched environmental concerns during the last two decades. Consequently, a large scientific knowledge-base has been developed on As distributions from local to global scales. However, differences in bulk sediment As concentrations cannot account for the As concentration variability in groundwater. Instead, in general, only aquifers in sedimentary basins adjacent to mountain chains (orogenic foreland basins) along continental convergent tectonic margins are found to be As-enriched. We illustrate this association by integrating observations from long-term studies of two of the largest orogenic systems (i.e., As sources) and the aquifers in their associated foreland basins (As sinks), which are located in opposite hemispheres and experience distinct differences in climate and land-use patterns. The Andean orogenic system of South America (AB), an active continental margin, is in principle a modern analogue of the Himalayan orogenic system associated with the Indus-Ganges-Brahmaputra river systems in South Asia (HB). In general, the differences in hydrogeochemistry between AB and HB groundwaters are conspicuous. Major-solute composition of the arid, oxic AB groundwater exhibits a mixed-ion hydrochemical facies dominated by Na-Ca-Cl-SO-HCO. Molar calculations and thermodynamic modeling show that although groundwater of AB is influenced by cation exchange, its hydrochemical evolution is predominated by feldspar dissolution and relationships with secondary clays. In contrast, humid, strongly reducing groundwater of HB is dominated by Ca-HCO facies, suggestive of calcite dissolution, along with some weathering of silicates (monosiallitization). This work demonstrates that although hydrogeochemical evolutionary trends may vary with local climate and lithology, the fundamental similarities in global tectonic settings can still lead to the elevated concentrations of groundwater As.