The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently circulating BA.2, raising concerns that it may further evade vaccine-elicited and therapeutic antibodies. We found BA.2.75 to be moderately more neutralization resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but more neutralization sensitive than BA.4/5 (0.6-fold). Relative to BA.2, BA.2.75 showed heightened resistance to class 1 and class 3 monoclonal antibodies targeting the spike-receptor-binding domain while gaining sensitivity to class 2 antibodies. Resistance was largely conferred by G446S and R460K mutations. BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, a therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited a higher binding affinity to host receptor ACE2 than other Omicron subvariants. BA.2.75 provides further insight into SARS-CoV-2 evolution as it gains transmissibility while incrementally evading antibody neutralization. Display omitted •BA.2.75 is more resistant to neutralization by polyclonal sera than BA.2•BA.2.75 shows heightened resistance to class 1 and class 3 RBD-directed antibodies•BA.2.75 is the first variant to show discernible resistance to bebtelovimab•BA.2.75 exhibits higher human ACE2-binding affinity than other Omicron subvariants Wang et al. have systematically evaluated the antigenic properties of the new SARS-CoV-2 Omicron subvariant BA.2.75. They found that BA.2.75 exhibits greater neutralization resistance to monoclonal antibodies and vaccine- and infection-induced sera than previous Omicron subvariant BA.2, while showing a higher binding affinity for human ACE2.