“This departure is a shock. It's a historic warning sign which must… be heard by all of Europe and make us reflect,” Macron said in a short televised address.
The French leader said he believed Brexit had been made possible because EU members had a tendency to “make Europe a scapegoat for our own problems”.
But while he had stern words for political leaders, for British people who have chosen to live in France, he was reassuring.
“I want to say to the British people who live here in France, sometimes for many years, that nothing will change tomorrow.
“Those people are at home in France today and will be tomorrow.”
Macron, who was elected on a promise to transform the EU, also argued that Britain's decision to leave was enabled by the fact that “we did not change Europe enough”.
Faced with competition from China and the US, “we need more Europe”, he went on, reiterating the themes of his historic Sorbonne speech of September 2017.
Calling Friday a “sad day” he attacked the “lies, exaggerations, simplifications and cheques promised that never arrived” of the Brexit referendum campaign of 2016.
“We must always remember where lies can lead our democracies,” he said solemnly.
Macron, who hosted the EU's Brexit negotiator Michel Barnier earlier Friday for talks in Paris, also sounded a firm note on the upcoming negotiations between London and Brussels on their future relationship.
While saying he hoped for the “closest, most solid, most enduring partnership possible” he warned: “It won't be the same as the relationship we have had for several decades.
“You cannot be both in and out.”