Johnson's support for the "Vote Leave" campaign presents a serious headache for Conservative leader and British Prime Minister David Cameron.
Cameron has been pushing for Britain to stay in the EU, and only last week struck a deal with the bloc's leaders to give the UK "special status." He's expected to address the House of Commons, the lower house of Parliament, on Monday, the first day of the formal referendum campaigning period.
Britons will vote in an "in or out" referendum on June 23
. Cameron argues the British economy will suffer if the country opts out.
In a 2,000-word opinion piece in the Telegraph on Sunday,
Johnson said leaving was a "once-in-a-lifetime chance to vote for real change."
"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.
In a press conference Sunday, Johnson said his decision to defy the prime minister's view caused "a huge amount of heartache."
"The last thing I wanted was to go against David Cameron or the Government," he said.
"I will be advocating Vote Leave or whatever the team is called -- I understand there are many of them -- because I want a better deal for the people of this country, to save them money and to take back control."
Prime Minister: Let us stay
Before Johnson showed his hand, Cameron appeared on Sunday morning television
to push for a vote to stay.
"If Boris and if others really care about being able to get things done in our world, then the EU is one of the ways in which we get them done," he said.
"Having that seat at the table in the EU -- just as being a member of NATO -- is a vital way that we project our values and our power and our influence in the world."
Britain is one of the biggest economies in the European Union -- and is a net contributor to the EU budget.
Critics say membership of the EU is a costly burden that brings regulations and excessive migration. Advocates say membership is good for the economy and leaving could be an expensive disaster.