Conor O'Shea says he "loved every minute" of being Italy head coach after deciding to step away from the role.
The Irishman had a contract through to May 2020 but has opted to resign with immediate effect.
O'Shea, a former London Irish and Harlequins coach, took over the Azzurri in March 2016, but Italy failed to make it out of the group stages of the recent Rugby World Cup.
"I loved every minute I spent in Italy and I really believe in what we have done and how it can be achieved in the years to come," O'Shea, who has been tipped to take up a position with the English Rugby Football Union, said via a statement on the Italian Rugby Federation's official website.
"We have started a process and generated a new, well-founded hope, but I also believe that the end of the Rugby World Cup represents the best time for everyone to make changes in view of the new cycle.
"I built friendships and made experiences that I will never forget. I sincerely hope to have left Italian rugby in a better position."
O'Shea's last match was the World Cup clash with South Africa, which ended in a 49-3 defeat to the eventual champions.
Italy needed to produce an unlikely victory over New Zealand in their final pool match in order to qualify – a fixture abandoned due to Typhoon Hagibis.