The UK's EU membership referendum is a "once-in-a-lifetime chance to vote for real change", Boris Johnson has argued as he declared support for an exit.
The London Mayor confirmed earlier to reporters that he would be campaigning to leave the union.
In a 2,000-word column for The Daily Telegraph, the Conservative MP said staying inside the union would lead to "an erosion of democracy".
The prime minister has said leaving the EU would be a "leap in the dark".
In his weekly column for the newspaper Mr Johnson commended David Cameron for doing "his very best" in securing a deal on renegotiated EU membership for the UK.
But he said that the EU "only really listen to a population when it says no".
"This is a moment to be brave, to reach out - not to hug the skirts of Nurse in Brussels, and refer all decisions to someone else," he wrote.
"This is the only opportunity we will ever have to show that we care about self-rule.
"A vote to Remain will be taken in Brussels as a green light for more federalism, and for the erosion of democracy."
Mr Johnson, who is the MP for Uxbridge and South Ruislip, is believed to have informed Mr Cameron of his decision to campaign for the UK to leave the union by text message shortly before making it public at 17:00 GMT.
BBC political editor Laura Kuenssberg said Mr Johnson's decision would be seen as a huge boost to the Out campaign and a major blow to the prime minister, who had hoped to persuade friends and rivals to back the campaign to remain.
In his column Mr Johnson added: "It is time to seek a new relationship, in which we manage to extricate ourselves from most of the supranational elements.
"We will hear a lot in the coming weeks about the risks of this option; the risk to the economy, the risk to the City of London, and so on; and though those risks cannot be entirely dismissed, I think they are likely to be exaggerated."
Addressing reporters outside his home in north London, Mr Johnson had said the EU was a "political project" that was in "real danger of getting out of proper democratic control".
Mr Johnson also denied his decision had anything to do with leadership ambitions, stressing that he had made up his mind "after a huge amount of heartache" and the last thing he wanted to do was defy Mr Cameron.
He said he would be backing the Vote Leave campaign - one of two groups seeking official designation as the exit campaign group - but ruled out taking part in TV debates against members of his party.
Meanwhile, Mr Johnson's father Stanley Johnson told BBC Radio 5 live he disagreed with his son's argument that the UK should leave the EU because it threatened British sovereignty.
He denied Mr Johnson's decision had been a "career move", saying he had "completely thrown away" any chance of a post inside Mr Cameron's cabinet by aligning himself against the prime minister.
Analysis, BBC deputy political editor James Landale
Boris Johnson is political box office. He is one of Britain's most charismatic politicians. So his decision to support Brexit gives popular appeal to a Leave campaign that has lacked a talismanic figurehead.
And polls suggest that his is a voice that many will listen to as they make up their minds. So the Mayor of London will transform the referendum campaign. But will he transform the result?
Until now Mr Johnson has won his votes as a jovial character in two regional elections. He is now testing his appeal on the national stage in a contest of historic importance. And that matters because Mr Johnson could be our prime minister one day.
Speaking to the BBC before Mr Johnson's announcement, Mr Cameron had issued a last-ditch plea to Mr Johnson to back staying in the EU.
He said if Mr Johnson cared about "getting things done" in the world, being a member of the EU was key.
And, he added, "linking arms" with Nigel Farage and George Galloway - part of the Grassroots Out movement which is also vying to become the official Leave campaign - was "taking a leap into the dark and is the wrong step for our country".
Mr Johnson's decision to back leaving the EU drew criticism from former Conservative Deputy Prime Minister Lord Heseltine, who called it "illogical".
"If it takes you this long to make up your mind about something so fundamental and you still have questions, then surely the right option is to stay with what you know rather than risk our economy and security with a leap in the dark," he said.
Among the cabinet members backing the Out campaign are Work and Pensions Secretary Iain Duncan Smith and Justice Secretary Michael Gove.
Zac Goldsmith, who is hoping to become Mr Johnson's successor as a Conservative London mayor in May, has also said he will vote to leave.