Trophoblast cell surface antigen 2 (TROP2) has been reported to be overexpressed in many cancers, and is involved in cancer cell proliferation, invasion, and metastasis. We previously developed a highly sensitive anti-TROP2 monoclonal antibody (mAb) (clone TrMab-6; mouse IgG2b, kappa) using a Cell-Based Immunization and Screening method. TrMab-6 is useful for investigations using flow cytometry, Western blotting, and immunohistochemistry and possesses antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against TROP2-expressing triple-negative breast cancer (TNBC) cell lines, such as MDA-MB-231 and MDA-MB-468. This study investigated whether TrMab-6 possesses in vivo antitumor activities via ADCC/CDC activities using mouse xenograft models of TNBC cell lines. In vivo experiments on MDA-MB-231 and MDA-MB-468 xenografts revealed that TrMab-6 significantly reduced tumor growth compared with normal mouse IgG treatment. The findings of this study suggest that TrMab-6 is a promising treatment option for TROP2-expressing TNBC.