An isolated monoclonal antibody that specifically binds human Claudin 18.2. A nucleic acid molecule encoding the antibody, an expression vector, a host cell and a method for expressing the antibody are also provided. The present disclosure further provides an immunoconjugate, a bispecific molecule, a chimeric antigen receptor, an oncolytic virus and a pharmaceutical composition comprising the antibody, as well as a diagnostic or treatment method using an anti-Claudin 18.2 antibody of the disclosure.