He will step down in May at the age of 62, earlier than the company's mandatory retirement age for CEOs of 65.
Mr Otellini, Intel's fifth chief executive, has worked at the company for nearly 40 years and became CEO in 2005.
Intel's board was surprised last week when Mr Otellini announced he planned to retire and it tried to get him to stay, Intel spokesman Chuck Mulloy said.
The firm, which has selected chief executives from within its own ranks throughout its 45-year history, said it would consider both internal and external candidates in a transition expected to last six months.
Mr Mulloy explained, due to the complex nature of Intel products, that internal candidates would still have an advantage.
But he added: "Good corporate governance dictates today you should look inside and out."
Wall Street experts said it might make sense for Intel to consider hiring an outsider to shake up its strategy, as the computing world goes through its most significant shift since the advent of the internet.
Since 2008, Intel's stock has fallen by more than 20%.
The firm's processors are dominant in personal computers, but it has been slow to expand into the fast-growing mobile industry.
"We all know that everyone is using smartphones and tablets now. It's the era of Intel versus Arm, so it may be good to come in with some fresh blood and a new perspective," Evercore analyst Patrick Wang said.
Intel also announced it was promoting three executives to become executive vice presidents.
They are: Renee James, who is in charge of Intel software; Brian Krzanich, who is chief operating officer and oversees manufacturing; and Stacy Smith, chief financial officer and director of corporate strategy.