Near-final results showed Mr Macron in the lead with 27.6 per cent of the vote, ahead of Ms Le Pen on 23.4 per cent, setting them up for an April 24 rematch of the presidential run-off in 2017.
Despite entering the campaign late and holding only one rally before the vote, Mr Macron slightly outperformed opinion polls and won immediate support from defeated rivals for the second round.
Far-left candidate Jean-Luc Melenchon was third with 22.0 per cent, while the candidates for France's traditional parties of government, the Socialists and the Republicans, were on course for humiliating defeats and historic low tallies.
Far-right commentator Eric Zemmour, a political newcomer, was on course for 7.1 per cent.
"It's a new campaign that is opening now," French Economy Minister Bruno Le Maire said after the publication of the projections, which led supporters of Mr Macron to erupt in joy at the candidate's headquarters in Paris.
The final-round duel between Mr Macron and Ms Le Pen is expected to be tighter than the run-off they fought in 2017, when he won with 66 per cent of the vote.
Ms Le Pen, bidding to be France's first woman president, looked on course for a higher first-round score than in 2017 when she won 21.3 per cent, and she will be able to pick up most of Mr Zemmour's votes in the second round.
"I will put France in order within five years," she told her supporters in Paris, urging "all those who did not vote for Emmanuel Macron" in the first round to back her in the second.
Mr Zemmour, who called each of his two million votes "a cry from a people that does not want to die", urged his supporters to back Ms Le Pen.
But Mr Macron, 44, swiftly won the support of the defeated Socialist, Communist, Green and traditional right-wing candidates for the second round.
Mr Melenchon urged his supporters to refrain from voting for Ms Le Pen, but did not issue a call to back Mr Macron.
About 48.7 million voters were eligible to vote after an unusual campaign overshadowed by Russia's invasion of Ukraine.
The projections are compiled by polling companies based on a sample of votes from stations especially chosen from across the country. They have proved to be highly accurate in past elections.
A pivotal moment in the next stage of the campaign is likely to come on April 20 when the two candidates are due to take part in a debate broadcast live on national television.
The final debate has in the past had a crucial impact on the outcome of the vote, such as in 2017 when Mr Macron was seen as gaining the upper hand in exchanges with a flustered Ms Le Pen.
He is expected for the next two weeks to put his diplomatic efforts on the Ukraine crisis to one side and focus more on campaigning in a bid to find the election momentum that has so far eluded his team.
Although her opponents accuse her of being an extremist bent on dividing society, Ms Le Pen has sought to project a more moderate image in this campaign and has focused on voters' daily worries over rising prices.
Anne Hidalgo, the Socialist mayor of Paris, was set for an estimated 1.8 to 2.0 per cent, a historic low for the Socialists who were in power just five years ago under president Francois Hollande.
Greens candidate Yannick Jadot was seen as winning 4.4 to 5.0 per cent and right-wing Republicans candidate Valerie Pecresse was projected to score an estimated 4.3 to 5 per cent.
This marks the third time that a far-right candidate has made the run-off vote of a French presidential election, including the 2002 breakthrough by Ms Le Pen's father, Jean-Marie, which shocked France, although he was ultimately defeated by Jacques Chirac.
Pollsters forecast that the final turnout would be about 76 to 74 per cent, down on 2017, although probably above the record-low turnout of just under 73 per cent in the first round of 2002.
The stakes are high for Mr Macron, who came to power aged 39 as France's youngest president with a pledge to shake up the country.
He would be the first French president to win a second term since Chirac in 2002.
If he does, Mr Macron would have five more years to push through reforms that would include raising the pension age to 65 from 62, against strong union opposition.
He would also seek to consolidate his number-one position among European leaders after the departure of German chancellor Angela Merkel.
A victory to Ms Le Pen would be seen as a triumph for right-wing populism, adding to election victories last weekend by Hungarian Prime Minister Viktor Orban and Serbian leader Aleksandar Vucic, both of whom have cordial ties with Russian President Vladimir Putin.
Mr Zemmour made a stunning entry into the campaign last year but has since lost ground.
Analysts say he has helped Ms Le Pen by making her appear to be more moderate.