The centre-right Republicans party is tipped to win the two-stage election in April and May
Macron, a former economy minister, finally ended speculation about his intentions by announcing his candidacy backed by his new centrist party, called "En Marche" ("On the Move").
Never elected and "neither of the left or the right" in his own words, the pro-business and technology-savvy former investment banker is hoping to shake up a race dominated by older, more familiar figures.
"We have entered a new era," Macron said Wednesday, referring to a crisis for Western democracies as well as the dangers of global warming and growing inequality.
"We can't respond with the same men and the same ideas," he added at a news conference held at a training centre in a gritty Parisian suburb.
The centre-right Republicans party is tipped to win the two-stage election in April and May, but some analysts are questioning such assumptions after Donald Trump's stunning upset in the United States.
Macron's entry adds another element of uncertainty, with the Republicans and ruling Socialist parties yet to nominate their candidates less than six months before the voting.
The resurgent far-right National Front under leader Marine Le Pen, who announced her slogan "In the name of the people" on Wednesday, is banking on new momentum after Trump's victory.
"Mr Macron is a candidate of the banks, there's always one," she said dismissively.
Macron, who quit the beleaguered Socialist government in August to focus on his own political movement, is expected to steal centrist voters from the Republicans as well as the left.
A poll Tuesday showed him as one of France's most "presidential" figures behind the election favourite Alain Juppe, a 71-year-old former prime minister with one of the longest CVs in French politics.
Juppe is seeking the Republicans' nomination ahead of ex-president Nicolas Sarkozy and former prime minister Francois Fillon, who polls show has made a late surge ahead of primary voting this Sunday and next.
Macron has a meagre two years in government on his CV, serving as a sometimes rebellious economy minister from 2014-2016 and time as an economic advisor to his one-time mentor, President Francois Hollande.
"I believe that the French people won't put their destiny in the hands of someone with no experience," Fillon said Wednesday.
But Macron believes youth and inexperience are assets in a country weary of a political class blamed for years of tepid growth, high unemployment and mounting government debt.
He quit Hollande's government in August and threw new barbs at his ex-boss and former colleagues in the Socialist party on Wednesday.
"I've seen the emptiness of our political system from the inside... I reject this system," he said.
He is left-wing on social issues, pledging to bring jobs to deprived areas, but also pro-business, notably as a vocal critic of France's strict labour laws.
"France will not build anything solid by leaving millions of people by the wayside," he said.
A maverick in politics as well as in his private life, the accomplished pianist is married to his former schoolteacher, a divorcee with three children who is some 20 years his senior.
President Hollande, who is yet to announce whether he will try to defy his disastrous ratings in next year's election, is reportedly furious at what he sees as betrayal by his one-time protegee.
The president called Tuesday for "cohesion" and "uniting" amid disarray in the Socialist party.
Hollande is one of the most unpopular president's since World War II after a five-year term marked by multiple terror attacks, stubbornly high unemployment and U-turns on policies.
He was widely criticised, even by his own prime minister, after agreeing to collaborate for a tell-all book published in October in which he criticised his own ministers, judges and the national football team.