President Giorgio Napolitano accepted the resignation and immediately scheduled talks with political party leaders Friday and Saturday. After that, he was 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 percent 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 Friday that fourth-quarter GDP edged up 0.
In a tweet Friday as he arrived at Napolitano's office, Letta said he was resigning and thanked "all those who have helped me."
Napolitano had tapped Letta in April, hoping he could lead long enough to enact sorely needed electoral reforms meant to make Italy more governable.
Those reforms are still on the table, but Renzi recently met with the Democrats' center-right rival, Silvio Berlusconi, to seek his support for a new electoral law that would try to end Italy's parliamentary paralysis.
Renzi's maneuver against Letta was stunning even by Italian standards, since he had long insisted that he would only go for the premiership via an election. But analysts said he saw an opportunity and seized it.
"Enrico Letta was not a bad prime minister, but he was not seen as getting things done," said James Walston, professor of politics at the American University of Rome. "Renzi promises to get things done. He promises to make the Democratic Party win and that is his biggest quality at the moment."
It's not clear how Italy's shifting political alliances will line up for the required vote of confidence in parliament once Renzi gets the nod from Napolitano, forms a government and outlines his agenda to kickstart the economy, create jobs and enact the electoral reforms.
The anti-establishment 5 Star Movement of comic-turned-politician Beppe Grillo—which wants to oust all of Italy's politicians—has already decided to boycott Napolitano's talks.
Tricia Thomas contributed.