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Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne viral pathogen that causes severe fever with thrombocytopenia syndrome (SFTS). The disease was initially reported in central and eastern China, then later in Japan and South Korea, with a mortality rate of 13–30%. Currently, no vaccines or effective therapeutics are available for SFTS treatment. In this study, three monoclonal antibodies (mAbs) targeting the SFTSV envelope glycoprotein Gn were obtained using the hybridoma technique. Two mAbs recognized linear epitopes and did not neutralize SFTSV, while the mAb 40C10 can effectively neutralized SFTSV of different genotypes and also the SFTSV-related Guertu virus (GTV) and Heartland virus (HRTV) by targeting a spatial epitope of Gn. Additionally, the mAb 40C10 showed therapeutic effect in mice infected with different genotypes of SFTSV strains against death by preventing the development of lesions and by promoting virus clearance in tissues. The therapeutic effect could still be observed in mice infected with SFTSV which were administered with mAb 40C10 after infection even up to 4 days. These findings enhance our understanding of SFTSV immunogenicity and provide valuable information for designing detection methods and strategies targeting SFTSV antigens. The neutralizing mAb 40C10 possesses the potential to be further developed as a therapeutic monoclonal antibody against SFTSV and SFTSV-related viruses. Author summary: Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is a tick-borne pathogen that causes severe illness known as SFTS. This disease has become a major health concern, particularly in China, Japan and South Korea, with a high mortality rate. Regrettably, there are currently no vaccines or effective treatments available for this disease. To address this critical gap, we developed three monoclonal antibodies (mAbs) targeting a specific region of the SFTSV glycoprotein. Among these mAbs, one, named 40C10, exhibited remarkable neutralizing activity against SFTSV as well as related viruses such as HRTV and GTV. It provided complete protection against disease and death in mice even when administered days after viral exposure. These findings are promising and suggest that mAb 40C10 has potential as a therapeutic option against SFTSV. This work is a significant step towards meeting the urgent need for effective treatments for SFTS. [ABSTRACT FROM AUTHOR]