Hydrothermal fluids have been suggested to be capable of leaching U and other elements (e.g., rare earth elements; REEs) from U-fertile granites to form granite-related U deposits. However, the nature and origin of the hydrothermal fluid responsible for transporting these elements are poorly constrained. Apatite accommodates both U and REEs, and its composition can be modified by hydrothermal fluids with certain compositions. This study investigated in situ chemical and Sr-Nd isotope compositions of primary apatite in altered wall granites from the Lujing U deposits in the Zhuguang batholiths. Large-scale alterations of apatite occurred during the hematitization stage. Uranium was extensively leached out of the apatite, and its total REE concentrations were decreased from as high as 12,667 ppm to a few hundred ppm during the alteration, whereas REE-bearing mineral inclusions were absent in altered apatites. The release of U and REEs was associated with decrease of Na, Mn, and Fe and increase of Ca, Cl, and Eu anomalies in altered regions of apatite. According to apatite compositional variations, the fluid that induced hematitization was oxidizing, rich in Ca and Cl, but poor in Na. The elevated Cl in the fluid is crucial for mobilizing both U and REEs, whereas can also be a major ligand for U6+ transport given the massive dissolution of apatite during the leaching process. Altered regions of apatite contain high radiogenic strontium, implying assimilation of the fluid by clastic sediments in the adjacent red-bed basins sourced from the Precambrian crystalline basement rocks. The oxidizing, Ca- and Cl-rich, but Na- and F-poor fluid that induces hematitization shows significant potential in leaching U and REEs from the wall granite and providing ore-forming materials for U mineralization.