The Tinto River estuary is one of the most contaminated coastal systems in the world due to the high amounts of pollutants this acidic river transports. The tidal influence and the fluvial discharges control the water mixing, which include a salt-induced process (that is typical of all estuaries) and an acid neutralization process (pH-induced mixing). These processes affect the geochemical behavior of uranium, which has a non-conservative pattern. Despite the high concentrations of dissolved uranium in the Tinto River, 234U/238U shows that uranium stems mostly from seawater (between 80 and 100%). Riverine uranium is adsorbed onto both Fe and Al precipitates when the acidic river water is mixed with seawater. Distribution coefficients (Kd) show that dissolved and particulate uranium are controlled by adsorption–desorption processes and the formation of carbonate complexes, both depending on pH. At low pH, uranium tends to be dissolved, and the adsorption by suspended particles is low. As the pH increases, the adsorption processes onto Fe and Al particles are more intense, increasing particulate uranium which reaches a maximum at pH 5.5, where the uranium solubility minimum occurs. At higher pH values, dissolved uranium increases by carbonate complexation.