The 38-year-old said he had "seen at first hand the limits of our political system" and that quitting the government of President Francois Hollande would enable him "to be free" to push forward his own agenda.
With elections eight months away, the former investment banker said: "I am determined to do everything so that our values, our ideas, our actions can transform France as soon as next year."
While Macron's resignation clears the way for a presidential bid, it is unclear how wide the appeal really is of such a young man who has never held elected office.
Today Macron charged that France's political system is broken, and that his movement called "En Marche" (On the Move) would put forward a "diagnosis" of the country's woes next month.
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Macron's departure is a blow to Hollande, whose approval ratings are the lowest of any post-war French president. He has pledged not to seek re-election if he fails to rein in stubbornly high unemployment, which is hovering at around 10 per cent.
Hollande has said he will not decide on a re-election bid until the end of the year.
Macron would be a fresh face in a presidential field that includes former president Nicolas Sarkozy, 61, and 71-year-old ex-prime minister Alain Juppe - both right-wing candidates.
Juppe is France's most popular politician, but Sarkozy is closing the gap fast. A poll this week showed both would score 34 percent in November's centre-right primary.
Marine Le Pen, 48, of the far-right anti-immigration National Front, is standing for a second time in presidential elections and many polls show she is likely to reach the second round of voting.
"I will then propose far-reaching action that can be taken," he said.
A maverick in politics as well as in his private life, Macron is married to a divorcee with three children who is some 20 years his senior.