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Macron was projected to win 23.9 percent in Sunday's first round, slightly ahead of National Front (FN) leader Le Pen with 21.7 percent, according to estimates on public television.
They will contest the run-off on May 7.
"I want to be the president of the patriots against the threat of nationalists," 39-year-old Macron told thousands of cheering supporters in Paris.
The euro rose sharply against the dollar and yen as the results emerged.
WATCH: Macron puts Le Pen in his sights
Macron, a former banker and economy minister whose marriage to his former school teacher has fascinated France, said the results were a clear rejection of France's traditional parties.
Neither candidate from the mainstream Republicans and Socialist parties made it through to the second round for the first time in six decades, in a major shakeup of national politics.
"The challenge is to break completely with the system which has been unable to find solutions to the problems of our country for more than 30 years," Macron added, already eyeing parliamentary elections in June.
The outcome capped an extraordinary campaign in a deeply divided and demoralised France, which has been hit by a series of terror attacks since 2015 and remains stuck with low economic growth.
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French centrist presidential candidate Emmanuel Macron thumbs as he addresses his supporters at his election day headquarters in Paris , Sunday April 23 (AAP) Source: AAP
New polls released Sunday evening showed pro-business Macron easily beating Le Pen, who has hardened her anti-immigration and anti-Europe rhetoric over the last week.
The French vote was being closely watched as a bellwether for populist sentiment following the election of Donald Trump as US President and Britain's vote to leave the EU.
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Throughout the campaign, Macron insisted France was "contrarian" -- ready to elect a pro-globalisation liberal at a time when rightwing nationalists are making gains around the world.
"It's a victory for openness, social-mindedness," Macron supporter Marie-Helene Visconti, a 60-year-old artist, told AFP at his election party where the EU flag was waved alongside the French tricolore.
WATCH: Le Pen hails 'historic' result
Le Pen follows father
Le Pen follows in the footsteps of her father Jean-Marie, who made it through to the 2002 presidential run-off in what came as a political earthquake for France.
Le Pen Senior went on to suffer a stinging defeat when mainstream parties closed ranks to keep him out.
Though projections showed Le Pen coming in behind Macron, there was joy at FN headquarters in Henin-Beaumont, northern France, with outbursts of the Marseillaise national anthem as supporters learned she had gone through to the run-off.
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Le Pen said the second round would be a battle over France's future. Her vision of a France out of the EU and behind reinforced borders is the opposite of Macron's.
"The major issue of this election is runaway globalisation, which is putting our civilisation in danger," she told supporters.
"Either we continue on the path of complete deregulation, with no borders and no protection... mass immigration and free movement of terrorists... or you choose France," she added.
Far-right expert Nonna Mayer at Sciences Po university said a Le Pen victory was not impossible, "but it seems unlikely that she will carry the second round".
"If she wins, it will obviously be an anti-Europe, protectionist, exclusionist line that wins and which could have troubling consequences for Europe and France," she added.
Despite Macron's plans to "relaunch the building of Europe", the combined scores of staunch eurosceptics Le Pen, far-left Jean-Luc Melenchon and nationalist Nicolas Dupont-Aignan add up to nearly 50 percent.
European Commission chief Jean-Claude Juncker on Sunday congratulated Macron and wished him "good luck".
Macron endorsements
Macron drew immediate support from his defeated rivals from the Socialists and Republicans.
Socialist Benoit Hamon, projected to win a humiliating six percent, said the left had suffered a "historic drubbing" but urged voters to keep out Le Pen who he said was "an enemy of the republic".
Scandal-hit Republicans candidate Francois Fillon followed suit, saying: "There is no other choice than voting against the far-right."
Fillon was seen as a favourite until January when his campaign was torpedoed by allegations that he gave his British-born wife a fictitious job as his parliamentary assistant.
He was on course Sunday to score 20 percent.
The former prime minister, 63, has accused Socialist President Francois Hollande of being behind a campaign to destabilise him and said in a concession speech the obstacles he had faced were "too numerous, too cruel".
Commenting on Macron's score, Philippe Braud, a veteran political observer and academic, said he had combined a strong campaign with a slice of luck.
"One must be lucky," he said. "He certainly benefitted from the fall of Fillon."
Support for Communist-backed Melenchon, meanwhile, had surged in recent weeks on the back of assured performances in two televised debates.
He was on course for around 19.2 percent of the vote, underlining the strength of anti-establishment sentiment.
High security
The vote took place under heavy security after the killing on Thursday of a policeman on Paris's Champs Elysees avenue claimed by the Islamic State group.
With France still under the state of emergency imposed after the Paris attacks of November 2015, around 50,000 police and 7,000 soldiers were deployed to guard voters.
Thursday's shooting on the best-known street in Paris was the latest in a bloody series of terror attacks that have cost more than 230 lives since 2015.
Nearly 47 million people were eligible to vote in the eurozone's second biggest economy and turnout was forecast to be high at around 80 percent. The results will be seen as a credit to French pollsters, who successfully forecast the results.
Watch: French voters set for presidential election
