The broadcaster announced the departure late Monday in a news release that said O'Leary had "made the decision to pursue new opportunities."
O'Leary partnered with his long-time BNN co-host Amanda Lang in 2009 to launch "The Lang & Leary Exchange."
The duo debated the top business stories of the day, with Lang often providing the opposing view to O'Leary's staunch support of free markets.
O'Leary had made a name for himself as an investor and businessman before becoming a television personality. Earlier this year, he said he was leaving the CBC reality series "Dragon's Den."
His remarks on "The Lang & O'Leary Exchange" occasionally sparked controversy, such as when he called an Oxfam report that showed the 85 richest people in the world had the same wealth as the 3.5 billion poorest people "fantastic news."
O'Leary, 60, called the public broadcaster "a national treasure" in the statement.
"I'm proud to have been part of its expanding role as a place where ideas that matter to Canadians can be debated from all sides," he said.
"At the CBC, I've had the opportunity to work with world-class producers and journalists, particularly Amanda Lang, with whom I enjoyed having so many intriguing and lively discussions over the years."
The CBC did not say whether O'Leary's departure was due to its ongoing budget struggles.
After announcing in April that 657 jobs would be cut due to a $130 million shortfall, the public broadcaster revealed last month that another 1,000 to 1,500 positions would be eliminated over the next five years.
The network said Lang would take the helm of a new business program replacing "The Lang & O'Leary Exchange" this fall.