The issue of low-frequency structural noise radiated from high-speed railway (HSR) box-girder bridges (BGBs) is a significant challenge worldwide. Although it is known that vibrations in BGBs caused by moving trains can be reduced by installing multiple tuned mass dampers (MTMDs) on the top plate, there is limited research on the noise reduction achieved by this method. This study aims to investigate the noise reduction mechanism of BGBs installed with MTMDs on the top plate. A sound radiation prediction model for the BGB installed with MTMDs is developed, based on the vehicle–track–bridge coupled dynamics and acoustics boundary element method. After being verified by field tested results, the prediction model is employed to study the reduction of vibration and noise of BGBs caused by the MTMDs. It is found that installing MTMDs on top plate can significantly affect the vibration distribution and sound radiation law of BGBs. However, its impact on the sound radiation caused by vibrations dominated by the global modes of BGBs is minimal. The noise reduction achieved by MTMDs is mainly through changing the acoustic radiation contributions of each plate of the bridge. In the lower frequency range, the noise reduction of BGB caused by MTMDs can be more effective if the installation of MTMDs can modify the vibration frequency and distribution of the BGB to avoid the influence of small vibrations and disperse the sound radiation from each plate.