Letta was sacked by his own party on Thursday in a back-room mutiny designed to catapult Florence's young mayor into the helm of Italy's government.
President Giorgio Napolitano accepted the resignation and immediately scheduled talks with political party leaders on Friday and Saturday.
After that, he is expected to ask the head of Letta's Democratic Party, Florence Mayor Matteo Renzi, to try to form a new government.
Letta is the third premier to fall from grace in as many years amid Italy's turbulent politics and economic crisis.
The country has a crushing unemployment rate, with some 40 per cent of young Italians jobless.
Renzi, meanwhile, spent Friday doing what he does best, being the popular, down-to-earth mayor who has used his outsider status on the national scene to project himself as a breath of fresh air for Italians fed up with the self-absorbed political class.
The 39-year-old presided over a Valentine's Day ceremony in Florence's city hall, feting Florentines celebrating their 50th wedding anniversaries.
A day earlier, he engineered a Machiavellian internal no-confidence vote in the party against Letta, accusing him of failing to lift Italy out of its economic and political doldrums.
Without the party's backing, Letta had no choice but to resign.
The timing of the ouster was ironic, given that the national statistics bureau Istat reported on Friday that fourth-quarter GDP edged up 0.1 per cent, the first positive growth since mid-2011.
In a tweet as he arrived at Napolitano's office, Letta said he was resigning and thanked "all those who have helped me".
Resignation of Italy's PM 'no surprise' to Aussie MP
A member of parliament representing Italians living in Australia says he's not surprised the country's Prime Minister, Enrico Letta, is resigning less than a year after his coalition government was formed following inconclusive elections.
Marco Fedi, who belongs to the same party of the outgoing leader, the centre-left Democratic Party, says Mr Letta wasn't seen as capable of standing up to the opposition.
On Thursday, an overwhelming majority of party members voted in favour of a motion requesting a change of government submitted by the party's secretary, 39-year-old Matteo Renzi.
Mr Renzi, who's the mayor of Florence but not a member of parliament, is now expected to become Italy's third unelected Prime Minister in less than three years.
Melbourne-based MP, Marco Fedi says Mr Letta did a good job in managing the country, but wasn't popular enough within his party ranks.
"Renzi has opened this discussion within the party, and Letta didn't survive within the party," Mr Fedi told SBS Radio. "So it is right to say that the Democratic Party has made this decision to give Renzi a chance...and now the ball is in his field.
"So, yes, the opposition was growing stronger and we needed a stronger leader. Maybe Letta was a good leader, but not sufficiently strong."
