The centrist's emphatic victory, which also smashed the dominance of France’s mainstream parties, will bring huge relief to European allies who feared another populist upheaval following Britain's vote to quit the EU and Donald Trump's election as US president.
Macron - the 39-year-old former investment banker who served for two years as economy minister but has never previously held elected office - will now become France's youngest leader since Napoleon with a promise to transcend outdated left-right divisions.
Three projections, issued within minutes of polling stations closing at 8pm (1800GMT), showed Macron beating Le Pen by about 65 percent to 35 - a gap wider than the 20 or so percentage points that pre-election surveys had pointed to.
"A new page in our long history has turned tonight," said Macron in a brief address to the press after the results were announced.
"I want it to be that of rediscovery of hope and trust."
He promised to "fight the divisions that undermine France" and to "rebuild the links between Europe and its citizens".
Al Jazeera's Natacha Butler, reporting from Macron headquarters outside the Louvre Museum, called his win "an extraordinary story".
"He only just launched his political movement a year ago, and so many people at the time said he was too young, that he had no political experience … and here he is, one year on, France’s youngest president."
Al Jazeera's Anealla Safdar was at Macron's headquarters when he won. Members of the crowd, celebrating the win, called it a "sign of hope" and urged the president-elect to unify the divided nation.
French political columnist Pierre Haski told Al Jazeera that Macron's win was "unprecedented".
"It's historical because it has blown up the political system. He's betting on his youth, on the energy and the optimism," he said.
Even so, it was a record performance for Le Pen's National Front (FN), a party whose anti-immigrant policies until recently made it a pariah in French politics, and underlined the scale of divisions that Macron must try to heal.
Le Pen called to congratulate Macron shortly after news broke of her defeat, telling her supporters and members of the press she wished the new president "success" even though he faces "huge challenges".
But, she added, her FN party needed to undergo a "profound transformation" in order to create a "new political force".
The far-right candidate's high-spending, anti-globalisation "France-first" policies may have unnerved financial markets, but they appealed to many poorer members of society against a background of high unemployment, social tensions, and security concerns.
"Marine Le Pen has tried to put a positive spin on her loss tonight," said Al Jazeera's senior political analyst Marwan Bishara. "She will remain an important figure in French politics."
The 48-year-old's share of the vote was set to be almost twice that won by her father Jean-Marie, the last National Front candidate to qualify for a presidential runoff, who was trounced by Jacques Chirac in 2002.
“Marine Le Pen now realises she is becoming the main opposition figure inside French politics," said Al Jazeera's David Chater, reporting from Le Pen headquarters in Paris.
Chater said Le Pen's FN was likely to turn its attention to the upcoming parliamentary elections in June.
“We have not heard the last from nationalism, we have not heard the last from the National Front and we have not heard the last from Marine Le Pen," he said.
Macron's immediate challenge will be to secure a majority in next month's election for En Marche! (Onwards!), his political movement that is barely a year old, in order to implement his political programme.
At least one opinion poll published in the run-up to the second round has indicated this could be within reach.
European Commission chief Jean-Claud Juncker hailed Macron's win in a post on Twitter, writing that the French had chosen "a European Future".
EU Council President Donald Tusk also offered his congratulations, saying the French had chosen "liberty, equality and fraternity" and "said no to the tyranny of fake news".
In a speech to thousands of his supporters later on in the evening, Macron made a plea for national unity.
"We will not give into fear, we will not give into division," he said, adding he would do everything to ensure that the French "had no reason to vote for extremes".
Source: Al Jazeera and news agencies