The role of the large-scale atmospheric circulation in producing heavy rainfall events and floods in the eastern part of Europe, with a special focus on the Siret and Prut catchment areas (Romania), is analyzed in this study. Moreover, a detailed analysis of the socio-economic impacts of the most extreme flood events (e.g., July 2008, June–July 2010, and June 2020) is given. Analysis of the largest flood events indicates that the flood peaks have been preceded up to 6 days in advance by intrusions of high Potential Vorticity (PV) anomalies toward the southeastern part of Europe, persistent cut-off lows over the analyzed region, and increased water vapor transport over the catchment areas of Siret and Prut Rivers. The vertically integrated water vapor transport prior to the flood peak exceeds 300 kg m-1 s-1, leading to heavy rainfall events. We also show that the implementation of the Flood Management Plan in Romania had positive results during the 2020 flood event compared with the other flood events, when the authorities took several precaution measurements that mitigated in a better way the socio-economic impact and risks of the flood event. The results presented in this study offer new insights regarding the importance of large-scale atmospheric circulation and water vapor transport as drivers of extreme flooding in the eastern part of Europe and could lead to a better flood forecast and flood risk management.