This study used observed rainfall, ERA5 reanalysis, and CMIP6 model datasets to investigate the interdecadal variation and underlying mechanism of persistent heavy rainfall (PHR) over the Huaihe River Basin (HRB) in China during July–August, and to examine the role of the Atlantic Multidecadal Oscillation (AMO) in modulating such rainfall. The results indicate that PHR over the HRB exhibited a marked interdecadal variation. The interdecadal increase in PHR was found attributable primarily to interdecadal enhancement of ascending motion, which might have been due to external forcing by the AMO. The AMO can trigger upper-tropospheric mid–high-latitude Rossby wave trains that can lead to an upper-tropospheric anticyclone and a lower-tropospheric cyclone configuration over the HRB. Increased warm advection and greater transport of water vapor from lower latitudes, caused by enhanced southerlies in the middle–lower troposphere over the HRB, can also lead to enhanced ascending motion over the HRB. Meanwhile, an anomalous cyclone over northeastern China triggered by AMO can transport cold air from higher latitudes to the HRB, boosting convection and promoting the development and duration of PHR. By affecting sea surface temperature in the western North Pacific Ocean, the AMO can also indirectly cause a meridional teleconnection pattern in the lower troposphere, which increases the transport of water vapor to the HRB. Numerical model experiments can reproduce both the interdecadal variations in PHR and the mechanisms of the influence of the AMO on PHR, providing a reliable foundation for understanding and forecasting PHR over the HRB.