"After a great deal of heartache... I will be advocating vote Leave," said Johnson, a popular politician from Cameron's own Conservative Party who is seen as a potential successor to the prime minister.
His comments will be seen as a key victory by supporters of Britain's departure from the EU -- or "Brexit" -- although Johnson in his comments implied he would not lead the movement and would not take part in frontline campaigning.
"There should be no confusion between the wonders of Europe and the holidays in Europe and fantastic food and friendships... With a political project that has basically been going on now for decades," he said.
He said the European Court of Justice's power "has been getting out of control" and called for "a new relationship" with the EU based on trade and cooperation.