Results from the first exit polls indicated a clear victory for the "No" campaign who rejected Mr Renzi's proposed changes to the Italian constitution.
Mr Renzi stepped down from his leadership as the results revealed his loss.
"My experience of government finishes here," he stated during a press conference at Palazzo Chigi in Rome.
Mr Renzi concluded the conference by thanking his wife and children for their effort and support over the past months.
With ANSA