Significance Due to their small size, nanobodies can recognize protein cavities that are not accessible to conventional antibodies. In this report, we built dromedary camel ( Camelus dromedarius ) V _H H phage libraries for the isolation of high-affinity nanobodies that broadly neutralize SARS-CoV-2 variants. Cryo-EM complex structures reveal that one dromedary camel V _H H nanobody (8A2) binds the S1 subunit of the viral spike protein, and the other (7A3) targets a deeply buried region that uniquely extends to the S2 subunit beyond the S1 subunit. These nanobodies can protect mice from the lethal challenge of variants B.1.351 or B.1.617.2, suggesting the therapeutic potential of these nanobodies against COVID-19. The dromedary camel V _H H libraries could be helpful to isolate neutralizing nanobodies against future emerging viruses quickly.