Fowl adenovirus serotype 4 (FAdV-4), leading to Hepatitis-hydropericardium syndrome (HHS) in chickens, has caused huge economic losses to the poultry industry in China since 2015. Therefore, effective therapeutic approaches to prevent FAdV-4 is critical for HHS control. In this study, we identified two monoclonal antibodies, 27A-5 and 42A-10, to specifically bind to and neutralize FAdV-4 viruses in vitro. Pre-incubation of both antibodies with FAdV-4 hindered the viruses from infecting LMH cells, with the complete blocking concentrations being 33.3 μg/mL for 27A-5 and 16.6 μg/mL for 42A-10. In addition, whether these antibodies pose viral neutralization abilities in vivo was determined, as was whether they could be used as therapeutic antibodies in the future. In chickens, the survival rates were 100% after administration with both antibodies (10 mg/kg), while the fatality rates of untreated chickens were 100%. In addition, a low dose (5mg/kg) of the 27A-5 antibody could save all animals. Moreover, pathologic changes such as pericardial sac liquid and liver damages in survivors were remarkably reduced. Further analysis demonstrated that inflammation caused by FAdV-4 infection was decreased in antibody treated animals. More importantly, the viral loads in treated chickens were almost cleared, indicating that the antibodies were effectively neutralizing the FAdV-4 viruses in vivo. In conclusion, the two antibodies could neutralize FAdV-4 in vitro and in vivo, which means that they have the potential to be therapeutic antibodies for HHS treatment. This study lays a foundation for the development of safe and effective therapeutic methods against FAdV-4.