Drinking water sources in the southeastern part of Lake Titicaca (Lower Katari Basin: LKB) and the southern part of Lake Poopó (Southern Poopó Basin: SPB) have high concentrations of arsenic (As), >10 μg/L compared to the WHO and NB-512 guideline value. These regions belong to the Bolivian Altiplano and are characterized by a semiarid climate, slow hydrological flow, with geological formations of volcanic origin, in addition to brines and other mineral deposits. The present study is focused on comparing the geochemical processes of As in relation to the sources and mobilization in groundwater (GW) in LKB and SPB. Groundwater (GW), surface water (SW) and sediment samples were collected from both basins. The As (LKB: 0.8–288 μg/L and SPB: 2.6–207 μg/L), boron (B) (LKB: 96–2473 μg/L and SPB: 507–4359 μg/L), manganese (Mn) (LKB: 0.6–7259 μg/L) and salinity (LKB: 125–11740 μS/cm) were found to be higher than the WHO guideline values, which is a serious concern about the GW quality for human consumption. The dissolution and exchange of bases are the processes that govern the mineralization of GW. Load of solids and liquids of anthropogenic origin in surface water (LKB) represents an environmental problem for communities on river banks. The spatial distribution of As was attributed to the geology of both the basins and the heterogeneously distributed evaporites in the sediments. The highest As concentrations are found in alluvial sediments of the northern region of LKB and “PACK belt” (an approximately 25 km long belt stretching along the southern shores of the Lake Poopó, between the villages of Pampa Aullagas and Condo K) in SPB. Sequential extraction of sediment and mineral saturation indices indicate that iron (Fe) and aluminum (Al) oxides as well as hydroxides are the most predominant mineral phases as potential sorbents of As.