A large number of lithium–potassium-rich brines have been found in Paleocene reservoirs in the Jianghan Basin, South China. First, the brines have exceptionally high lithium and potassium contents that are even higher than those in other closed basins on the Tibetan Plateau. Second, the enriched brines are widely distributed in the center of the basin. The Mesozoic and Cenozoic igneous rocks in the Jiangling depression are mainly basalt and granite, and their distribution area exceeds 50% of the basin. The large basalt body provided a thermal source for the water–rock reaction. The igneous rocks in the study area could have provided ore-forming elements, such as lithium and potassium, for the brine. A static immersion experiment at room temperature shows that fluids with certain salinities are more likely to activate K ions in basalt. However, weakly alkaline solutions more easily dissolve K. High-temperature water–rock experiments show that the dissolution rates of Ca, Mg, and Sr decrease with increasing temperature, while the dissolution rates of K and Li first increase and then decrease with increasing temperature. The dissolution of K and Li is easier when saline fluid reacts with volcanic rock. The dissolution rate of K is higher than that of Li in basalt, and the dissolution rate of Li is higher than that of K in granite. Compared with the results at normal temperatures, the ability of the fluid to leach elements at higher temperatures is significantly enhanced. Temperature is the main factor controlling the ability of fluid to leach elements. High-salinity fluid is the main carrier of ore-forming elements. According to the water–rock experiments, the mineral composition of the ancient brine in the Jiangling depression that formed during the Paleocene is consistent with that of the ore-rich brine found today, but different by a few orders of magnitude, indicating that the formation of lithium–potassium-rich brines requires a long time. The water–rock reaction is one of the important processes of brine formation, and surface evaporation and concentration are the main mechanisms of brine mineralization.