Abstract: In 2021, the Yellow River underwent the most serious autumn flood since the foundation of New China, during which the safety of flood control in the Lower Yellow River（LYR） was greatly threatened. It provides a rare opportunity to investigate how to make effective decisions on dealing with extreme floods, which is urgently needed for river management departments. The most dangerous reach of the LYR, the Kaifeng reach, is selected as the study object. Based on the measured flow data from the upstream hydrological stations and the topographic data of local reach, the characteristics of the 2021 autumn flood in the Kaifeng reach are analyzed. Then some successful practical experience about defending against the extreme flood, characterized by high flow, long duration and high water level, is summarized. Firstly, the “one center, two key points, three things that can’t happen, four measures to put in place, five transformations” basic principles of flood control were followed. Secondly, the flood defense mechanism of “leading of the party and government, emergency coordination, support of river administration bureau, departmental cooperation, group prevention and control” was adopted. Thirdly, four resettlement types of “self-owned housing, stay with relatives and friends, mutual help among residents, centralized resettlement” for the people who live on the floodplain of the Yellow River was sorted out. Fourthly,the defense measures of “plan before the river regime changes, prevention in the beginning of the danger, protection of key zones of river projects” were innovatively implemented. Lastly,the party branch played an important role. The above practical experience has proved to be effective, not only for the future flood control of the Yellow River, but it is also replicable and extendable, which is of great significance to flood safety management in other rivers.