Letta vowed to bring political stability and economic growth to a country on the point of exiting its longest post-war recession, condemning "chaos" after anti-austerity protests this week across Italy.
"We will not allow Italy to sink again," Letta told lawmakers, promising to "fight with everything I have to avoid our country being thrown back into chaos just as it is beginning to lift itself up again".
"Today we are drawing a clear line. On this side are those who love Europe... Knowing that without the European Union we would plunge into the Middle Ages.
Letta won the vote in the lower house handily with 379 in favour and 212 against and was expected to get a majority, although by a far narrower margin, in a vote in the upper house scheduled for later on Wednesday.
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Letta admitted that instability had "weakened" his government but voiced hope that the confidence vote would give his coalition a stronger mandate to govern and press ahead with much-needed reforms.
He said he would impose further cuts on Italy's overweight bureaucratic machine and aim for gross domestic product (GDP) growth of 1.0 per cent in 2014 and 2.0 per cent in 2015, while also slashing debt.
Letta also promised to reduce the number of parliamentarians and end public subsidies to political parties -- both reforms that have long been mooted in Italy including by Letta but never carried out.
The vote was called after the scandal-tainted Berlusconi's party quit the ruling coalition and he was ejected from parliament over a tax fraud conviction.