Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a serious impact on people’s health and lives. At present, SARS-CoV-2 is still widely spread, but effective treatments for SARS-CoV-2 are still limited. Therefore, it is of great significance to find broad-spectrum neutralizing antibodies to block SARS-CoV-2 infection. In this study, we successfully expressed and purified three human-mouse chimeric antibodies targeting receptor-binding domain (RBD) of SARS-CoV-2, and then the neutralizing activities of these antibodies against a variety of SARS-CoV-2 pseudoviruses and authentic virus were tested. The results showed that these three antibodies could specifically neutralize SARS-CoV-2 wild-type pseudovirus, and the IC50 values were 0.03 μg/mL, 0.06 μg/mL and 0.03 μg/mL, respectively. Furthermore, these antibodies exhibited broad-spectrum neutralizing activity against Alpha, Delta and Lambda pseudoviruses, and could also inhibit the replication of SARS-CoV-2 Delta authentic virus. Mechanism studies showed that these antibodies could block cell-cell fusion mediated by SARS-CoV-2 S protein, and K417, E484 and N501 on receptor-binding domain (RBD) may be the key sites for binding with these three antibodies.