The likely result clears the way for a straight two-way fight between the pair in a second and final round on May 7, with opinion polls saying Macron is the favourite.
Here are some of the first reactions to sunday's vote:
European Commission head Jean-Claude Juncker congratulated the pro-EU Macron after projections showed him ahead in the first round and wished him "good luck" in the run-off.
Chancellor Angela Merkel's spokesman wished Macron "all the best for the next two weeks".
"It's good that Emmanuel Macron was successful with his course for a strong EU and social market economy," Steffen Seibert said in a tweet.
Foreign Minister Sigmar Gabriel predicted that the 39-year-old Macron would be the next president of France.
"I'm sure he will sweep away the far-right, right-wing populism and the anti-Europeans in the second round," Social Democrat Gabriel said in a video posted on Twitter during a trip to Jordan's capital Amman.
Writing on Twitter, he added: "I'm glad that @EmmanuelMacron is leading the field. He was the only truly pro-European candidate."
Former Conservative finance minister George Osborne, recently appointed editor of London's Evening Standard newspaper, hailed a good result for the centre.
"Congratulations to my friend @EmmanuelMacron. Proof you can win from the centre. At last, the chance for the leadership that France needs," he tweeted.
Prime Minister Lars Lokke Rasmussen expressed cautious optimism that former banker Macron would emerge victorious over Le Pen.
"Congratulations @EmmanuelMacron. We should await the final election, but Europe needs an openminded and reform oriented France => Good luck!"
Norwegian Foreign Minister Borge Brende, whose country is not a member of the European Union, tweeted: "We need more not less cooperation in #Europe. Positive that @EmmanuelMacron is projected to win first round of #franceelections.
Geert Wilders, Dutch MP and leader of the anti-Islam anti-immigrant Freedom Party, swung behind Le Pen, welcoming the result as a "bright day for patriots in France and elsewhere who want more national sovereignty and less EU and immigration.
"I have just sent him my sincere congratulations. Now on the way to a vigorous second round, I am hoping for a President Le Pen."