Sabkha Matti is a potential discharge point for regional groundwater systems in the Rub’ al Khali topographic basin of Saudi Arabia. The hydrogeochemical evolution of this sabkha (salt flat) and the underlying aquifers were assessed by using a combination of geological, hydraulic, hydrochemical, and isotopic approaches. A compilation of the geologic structure and lithology in combination with boron isotope data attributed the origin of salinity in the regional aquifers underlying Sabkha Matti to the entrapment of ancient seawater in a coastal lagoon environment during the depositional time of the late Oligocene-Miocene formations. Major ionic constituents and strontium isotope ratios from the trapped paleo-seawater were observed to resemble those obtained from the near-surface sabkha brine. These data, along with hydrostatic head measurements, suggest that the origin of the solutes in Sabkha Matti is associated with brines ascending from the underlying formations. The data also show that solute concentrations in Sabkha Matti are increasing over time through a combination of evaporation, mineral dissolution by recharge, and a density-driven convection mechanism that circulates the solutes. On the other hand, stable isotopes of water (δ18O, δ2H) and radio isotope data (14C and 3H) suggest that the existing waters in the sabkha and the underlying aquifers are relatively recent and were recharged during the wet phase in the late Pleistocene-Holocene between 3,200 and 14,000 BP. This study shows that the water and solutes in Sabkha Matti area are a combination from different sources.