A human monoclonal antibody, S309, derived from memory B cells of an individual infected with SARS-CoV in 2003, exhibits broad cross-neutralizing activity against both SARS-CoV and SARS-CoV-2. S309 targets the receptor-binding domain (RBD) of the S glycoprotein of SARS-CoV-2, which is conserved within the Sarbecovirus subgenus. Cryo-electron microscopy and binding assays reveal that S309 recognizes an epitope containing a glycan that is conserved in Sarbecoviruses, without competing with receptor attachment. When combined with other antibodies, S309 enhances SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. The structural basis of S309's cross-neutralization involves recognition of a proteoglycan epitope on the SARS-CoV-2 S glycoprotein, distinct from the receptor-binding motif. S309's epitope is highly conserved between SARS-CoV and SARS-CoV-2, allowing it to neutralize both viruses. The antibody also recruits effector mechanisms, such as antibody-dependent cell cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), which contribute to its neutralizing activity. S309's ability to neutralize SARS-CoV-2 is further enhanced when combined with other antibodies, such as S304 and S315, which target different antigenic sites on the S glycoprotein. These findings suggest that S309 and antibody cocktails containing S309 could be used for prophylaxis in high-risk individuals or as post-exposure therapy to limit or treat severe disease. The study highlights the potential of monoclonal antibodies in combating SARS-CoV-2 and underscores the importance of understanding the structural and functional characteristics of viral antigens in the development of effective therapeutic strategies.A human monoclonal antibody, S309, derived from memory B cells of an individual infected with SARS-CoV in 2003, exhibits broad cross-neutralizing activity against both SARS-CoV and SARS-CoV-2. S309 targets the receptor-binding domain (RBD) of the S glycoprotein of SARS-CoV-2, which is conserved within the Sarbecovirus subgenus. Cryo-electron microscopy and binding assays reveal that S309 recognizes an epitope containing a glycan that is conserved in Sarbecoviruses, without competing with receptor attachment. When combined with other antibodies, S309 enhances SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. The structural basis of S309's cross-neutralization involves recognition of a proteoglycan epitope on the SARS-CoV-2 S glycoprotein, distinct from the receptor-binding motif. S309's epitope is highly conserved between SARS-CoV and SARS-CoV-2, allowing it to neutralize both viruses. The antibody also recruits effector mechanisms, such as antibody-dependent cell cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), which contribute to its neutralizing activity. S309's ability to neutralize SARS-CoV-2 is further enhanced when combined with other antibodies, such as S304 and S315, which target different antigenic sites on the S glycoprotein. These findings suggest that S309 and antibody cocktails containing S309 could be used for prophylaxis in high-risk individuals or as post-exposure therapy to limit or treat severe disease. The study highlights the potential of monoclonal antibodies in combating SARS-CoV-2 and underscores the importance of understanding the structural and functional characteristics of viral antigens in the development of effective therapeutic strategies.