Significance Since SARS-CoV-2 emerged in China, it has spread rapidly around the world. Effective vaccines and therapeutics for SARS-CoV-2−induced disease (coronavirus disease 2019;COVID-19) are urgently needed. We found that SARS-CoV-2 isolates replicate efficiently in the lungs of Syrian hamsters and cause severe pathological lesions in the lungs of these animals similar to commonly reported imaging features of COVID-19 patients with pneumonia. SARS-CoV-2−infected hamsters mounted neutralizing antibody responses and were protected against rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters inhibited virus replication in their lungs. Syrian hamsters are a useful small animal model for the evaluation of vaccines, immunotherapies, and antiviral drugs.