In what analysts expected to be a smooth transition, Chief Operating Officer Don Thompson, 48, will succeed Skinner, effective July 1, becoming one of the most prominent African-American CEOs in the United States.
Skinner, 67, has led McDonald's since November 2004 and is widely credited with executing the turn-around of the ubiquitous fast-food chain, whose shares more than tripled while he was CEO.
He also will resign from the board of McDonald's.
The company did not give a reason for Skinner's departure, but analysts said the move, while not entirely a surprise, came earlier than expected.
My suspicion is that he thinks the company is in a really good spot ... and that with Don, the company is in good hands. He's done what he set out to do, said RBC Capital Markets analyst Larry Miller.
Jim's not going to hang around. That's his style, Miller said, referring to him as a no-nonsense CEO.
Analysts said Thompson - who previously oversaw the company's U.S. operation and is credited with its widely successful domestic roll-outs of lattes, frappes and other beverages - should be up to the task.
Don Thompson has proven himself to be an excellent operator and a strong manager, which should help assuage investor concerns, Bernstein Research analyst Sara Senatore said.
Everything Don's done has been a home run, RBC Capital Markets' Miller said. I don't see McDonald's missing a beat.
Shares in the company barely budged in extended trading following the news, slipping 0.1 percent to $96.60.
TOUGH START AT THE TOP
Skinner began his career as a restaurant manager trainee in Illinois and quickly worked his way up the ranks of the company's U.S. unit.
He joined the McDonald's international management team in 1992 and was vice chairman in charge of McDonald's operations in Asia, the Middle East, Africa and Latin America when he was promoted to CEO - the company's third in one year.
McDonald's Chief Executive Jim Cantalupo died of a heart attack in April 2004, shortly before he was to speak to thousands of McDonald's owners and operators. His successor Charlie Bell was diagnosed with colorectal cancer just weeks into his tenure and stepped down in November that same year.
Skinner wasn't in the post long when Super Size Me, a scathing documentary about McDonald's and the fast-food industry, hit theaters.
The company ended the practice of super-sizing after a public outcry. It also expanded its menu with low-priced and premium food, extended operating hours and remodeled units, moves that contributed to a nearly nine-year run of rising sales at established restaurants.
Thompson, a Purdue University alumnus, takes the No. 1 job at a time when the company, valued at close to $100 billion, is outpacing competitors and its stock is trading near record highs.
The Chicago native joined McDonald's in 1990 as an electrical engineer. He climbed the ranks to become the company's U.S. president before his elevation to COO in 2010, after which he oversaw overall strategy and operations for more than 30,000 restaurants across the globe.
When Thompson - who is often hailed as an African-American role model - was appointed COO, some on Wall Street saw him as a clear front runner to one day run the company.
(Reporting by Lisa Baertlein in Los Angeles; Additional reporting by Matt Daily in New York, Brad Dorfman in Chicago, Edwin Chan in San Francisco and Ankur Banerjee in Bangalore; Editing by Edmund Klamann)