Named after the high-visibility safety jackets they wear, the protesters have become a new symbol of opposition to the 40-year-old centrist whose popularity has plumbed new depths in recent weeks.
The so-called "yellow vests" claim to stand up for persecuted motorists, represented by an accordion-playing former clairvoyant from northwest Brittany.
In a sign that their threat is being taken seriously, Interior Minister Christophe Castaner warned Tuesday that authorities would not tolerate roads being paralysed, telling BFM television the protest was "irrational".
Many drivers claim to be suffering from anti-car policies which spare wealthy and urban elites who are either immune to, or less concerned by Macron's policy changes.
These include higher taxes on diesel, lower speed limits, more speed radars and stricter pollution controls -- all introduced in the name of better safety or cutting pollution.
"When is this hounding of drivers, which you've pursued since your arrival, going to end?" Jacline Mouraud, a Brittany motorist, said in a wildly popular YouTube tirade.
After widespread media coverage, Mouraud has emerged as the unlikely face of the "yellow vests", who follow in a long history of protest movements sparked by tax grievances in France.
These include the Breton "Red Caps" of the 17th century, Pierre Poujade's crusade against the "fiscal Gestapo" in the 1950s or more recently a revolt by Brittany business chiefs which forced officials to scrap a pollution tax on trucks.
Mouraud is an accordionist who once offered spiritualism sessions involving "ectoplasm", a substance with no proven existence but which supposedly gives shape to paranormal energy.
She has also expressed alarm over so-called "chemtrails" left by airplanes, a favourite of conspiracy theorists who say governments are spraying any number of chemicals over their citizens.
After claiming that officials are earning millions from increased speeding tickets and higher fuel taxes, she asks in her video: "What are you doing with the dough, besides changing the Elysee's china or building yourself a swimming pool?"
Those episodes -- a pricey presidential tableware order and a pool at a summer residence -- were among a handful of incidents that have reinforced Macron's reputation as a "president of the rich".
The former investment banker's popularity remains at record lows with less than 30 percent of respondents rating him favourably in various polls.
Macron maintains he is acting on his mandate to transform France after years of complacency, and insists he is willing to risk voters' wrath while pushing through his reforms.
"The same people complaining about fuel prices also want us to fight air pollution because their children are falling ill," he told a group of regional newspapers this month.
Tax on diesel has risen around 23 percent over the past twelve months, compared with 15 percent for standard fuel.
At an average of 1.51 euros per litre, diesel is now more costly than at any point since the early 2000s.
Officials argue that the rise is linked to the international price of oil, which has soared due to tensions in the Middle East, with taxes accounting for only around a third of fuel prices.
But analysts say Macron may have failed to grasp the widespread ire of "deep France", the rural areas which have been hit hard by economic upheaval and budget cuts that have crimped public services.
These areas voted overwhelmingly for Macron's opponents, particularly for the far right, in last year's presidential contest.
"Populations far from the big urban centres or stuck on the bottom of the social ladder feel a sense of fiscal injustice," said Alexis Spire of the CNRS research institute.
Faced with the prospect of millions of people blocking roads, Prime Minister Edouard Philippe's office said measures to ease the pain for motorists who need their vehicles for work would be announced Wednesday morning.
That may be too late to quell the "yellow vests", which have capitalised as well on anger over tax increases for retirees amid fiscal relief for businesses and high-earners.
And the uncertainty about who is orchestrating the blockade makes it harder for Macron to defuse the revolt.
"The government and the head of state have everything to fear from a movement that incorporates not only drivers, but all those who feel left behind as costs of living rise," the Eclair des Pyrenees newspaper wrote in an editorial Tuesday.