A warming climate may increase flood hazard through boosting the global hydrological cycle. However, human impact through modifications to the river and its catchment is not well quantified. Here, we show a 12,000-year-long record of Yellow River flood events by synthesizing sedimentary and documentary data of levee overtops and breaches. Our result reveals that flood events in the Yellow River basin became almost an order of magnitude more frequent during the last millennium than the middle Holocene and 81 ± 6% of the increased flood frequency can be ascribed to anthropogenic disturbances. Our findings not only shed light on the long-term dynamics of flood hazards in this world’s most sediment-laden river but also inform policy of sustainable management of large rivers under anthropogenic stress elsewhere.