Uranium (U) contamination of terrestrial and aquatic ecosystems poses a significant threat to the environment and human health due to the chemotoxicity of this actinide. The characterization of organisms that tolerate and accumulate U is crucial to decipher the mechanisms evolved to cope with the radionuclide and to propose new effective strategies for the bioremediation of U-contaminated environments. Here, we isolated a unicellular green microalga of the genus Coelastrella from U-contaminated wastewater. We showed that Coelastrella sp. PCV is much more tolerant to U than Chlamydomonas reinhardtii and Chlorella vulgaris. Coelastrella sp. PCV is able to accumulate U very rapidly and then gradually release it into the medium, behaving as an excluder to limit the toxic effects of U. The ability of Coelastrella sp. PCV to accumulate U is remarkably high, with up to 240 mg of tightly bound U per g of dry biomass. Coelastrella sp. PCV is able to grow and maintain high photosynthesis in natural metal-contaminated waters from a wetland near a reclaimed U mine. In a single one-week growth cycle, Coelastrella sp. PCV is able to capture 25-55% of the U from the contaminated waters and shows lipid droplet accumulation. Coelastrella sp. PCV is a very promising microalga for the remediation of polluted waters with valorization of algal biomass that accumulates lipids.