"What we are currently experiencing is the brain death of NATO," the BBC reported citing Macron as saying in an interview to The Economist on Thursday.
He warned European members that they could no longer rely on the US to defend the alliance, established at the start of the Cold War to bolster Western European and North American security.
Article Five of NATO's founding charter stipulates that an attack on one member will produce a collective response from the alliance.
But Macron appeared unsure whether it was still valid when asked as he replied "I don't know".
The alliance, Macron said "only works if the guarantor of last resort functions as such. I'd argue that we should reassess the reality of what Nato is in the light of the commitment of the US".
The French leader urged Europe to start thinking of itself as a "geopolitical power" to ensure it remained "in control" of its destiny.
Responding to Macron's remarks, German Chancellor Angela Merkel, while speaking in Berlin alongside visiting NATO Secretary-General Jens Stoltenberg, said the French President "used drastic words - that is not my view of co-operation in NATO", reports the BBC.
Merkel acknowledged that there were problems, but said she did not think that "such sweeping judgements are necessary".
Stoltenberg said the alliance remained strong, adding that "European allies are stepping up, investing more in defence".
Also reacting to Macron was Russia's Foreign Ministry spokeswoman Maria Zakharova, who said in a Facebook post: "Well said. Truthful words, and ones that get to the nub of the matter... An accurate description of NATO's current state."
NATO members were taken by surprise when US President Donald Trump abruptly decided to pull most US forces out of north-eastern Syria in October.
The move paved the way for Turkey, also a powerful NATO member, to push into Syria and create what it termed a security zone along its border.
( With inputs from IANS )