Dissolved uranium in groundwater contaminated by acid in situ leaching poses a serious threat to human health and the ecosystem due to its toxicological properties. In this article, carboxy methyl cellulose (CMC) with high dispersity was used to stabilize nano zero-valent iron (nZVI), and highly dispersed CMC-stabilized nZVI (CMC-nZVI) was synthesized by a liquid-phase reduction method, characterized by multiple analysis techniques, and tested for its dispersal and antioxidizing properties. Compared with nZVI, CMC-nZVI showed great dispersal and resistance to oxidation. The effects of oxygen, pH, dosage, initial U(VI) concentration and HA concentration on U(VI) elimination by CMC-nZVI, and the U(VI) removal kinetics and mechanism were investigated. The removal capacity of U(VI) by CMC-nZVI was 400 mg g−1 at pH 3.0, and the dose of 0.1 g L−1 showed excellent uranium removal efficiency under acid conditions. Moreover, CMC-nZVI was used to treat groundwater from an area after acid in situ leach uranium mining, and CMC-nZVI was found to be capable of decreasing the concentration of uranium in the acidic groundwater (pH < 3) from 0.321 to 0.001 mg L−1. The results indicate that CMC-nZVI has potential application prospects in the in situ remediation of groundwater in areas after acid in situ leach uranium mining.