Mr Renzi had said he would step down if Italians dismisses his arrangement to lessen the part of the Upper House Senate and hook back forces from provincial powers.
He said regardless of the misfortune he was glad for his supporters.
"We've fought with passion from the very first day," Mr Renzi said.
"You know what I said and my Government ends here, today."
He said he assumed full liability for the "extraordinarily clear" thrashing and that on Monday evening he would meet his bureau and after that deliver his renunciation to President Sergio Mattarella.
Leave surveys appeared around 60 for every penny of Italians voted against Mr Renzi's changes and early voting outcomes proposed his "Yes" camp may have lost the submission by as much as 20 focuses.
A leave survey by the Piepoli Institute/IPR for state TV channel RAI, had assessed those voting Yes to back the change at 42-46 for every penny, contrasted and 54-58 for each penny for No.
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