The rapid emergence of the COVID-19 pandemic, and the SARS and MERS epidemics within the past two decades highlight coronaviruses as critically important human pathogenic viruses with pandemic potential. Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Our strategy is to use therapeutic monoclonal antibodies to disrupt coronavirus entry. Alpacas and llamas have evolved diminutive antibodies called nanobodies, which are the smallest naturally derived single domain antibodies. Nanobodies are of interest due to their small size, high antigen binding affinity, increased stability and their ease of manufacturability. Their special features have driven their increased development as treatments and diagnostics against human diseases, as versatile imaging tools for tracking single molecules to tumours, as crystallization chaperones to high precision discovery research tools. We show that nanobodies block virus entry into cells and suppress virus infection in mouse models. Using both cryo-EM and X-ray crystallography approaches, our structural findings reveal the fine specificities of neutralizing nanobodies associated with multiple distinct sites on SARS-CoV-2 proteins. These structural blueprints identify complementary antibodies for rational design of therapeutic cocktails against COVID-19.