Initial estimates showed Macron winning between 65.5 percent and 66.1 percent of ballots ahead of Le Pen, who is expected to win between 33.9 percent and 34.5 percent.
In an interview with AFP, Macron said his election victory represented “hope” and a “new chapter” for France.
“A new chapter in our long history begins tonight. I want it to be one of hope and renewed confidence,” he added.
Defeated candidate, Marine Le Pen, claimed a “historic, massive result” for her far-right National Front (FN) in Sunday’s presidential run-off, AFP reported.
Le Pen made a short statement, saying she had called Macron to wish him “success” in tackling the “huge challenges” he faced.
Le Pen also announced that she would lead the FN into June’s legislative elections.
People in France started to cast their ballots in the presidential run-off earlier on Sunday after polling stations opened at 8 a.m. local time (0600 GMT).
Some 47 million people were eligible to vote at 66,546 polling stations across the European countries.
Figures from the Interior Ministry said 65.30 percent of voters had turned out by 5 p.m. (1500 GMT), which was lower than in any of the past four presidential elections at the same stage of the day, Reuters reported.
Pollsters’ estimates based on these figures put the final turnout at 73-75 percent, down from around 80 percent or more in those past four elections.
Macron and Le Pen won the first round of voting in France’s presidential election on April 23. Macron finished first with 24 percent, ahead of Le Pen with 21.3 percent.
The populist far-right candidate has portrayed herself as anti-EU, anti-NATO, and anti-immigration.
Macron is seen as a centrist who aims to continue the policies of outgoing President Francois Hollande by deregulating the economy and deepening integration with the European Union.