The flood history of the Arno River, Italy, is initially described in the wider context of the river system evolution and its interactions with natural and human causes, with particular attention to the last two millennia. A description of the flood history is then reported, using the original data of Morozzi (1762) integrated with more recent data. Eight flood events can be defined as exceptional, but Florence was also inundated in 48 other minor floods. The flood of 4 November 1966 is described in detail, with particular focus on the meteorological causes that determined the exceptionality of the event. After the flood of 1966, other significant events occurred in 1992 over the whole Arno watershed, particularly upstream of Florence. The prevention measures (structural and non-structural measures for flood mitigation) carried out from 1966 to the present day are also described.