News Corp boss Rupert Murdoch has filed for divorce from Wendi Deng because their marriage has "irretrievably broken down", his spokesman says.
The divorce papers were filed at the New York State Supreme Court.
The couple, married in 1999 aboard a private yacht in New York, have two daughters together, Grace and Chloe.
In 2011, Ms Deng famously leapt to her husband's defence to slap a protester who threw a pie at him as British MPs quizzed him over phone-hacking.
Mr Murdoch, 82, met his Chinese-born third wife in 1997 at a cocktail party in Hong Kong. They were married two years later, weeks after his second divorce.
Ms Deng, 44, is 38 years younger than the Australian-born media mogul, who is said by Forbes to be worth $9.4bn (£6bn).
"I can confirm for the record that Rupert filed in New York State Supreme Court this morning for divorce," Murdoch spokesman Steven Rubenstein told AFP news agency on Thursday.
The BBC's Robert Peston says the couple had a pre-nuptial agreement and have held shares in trust for their children.
So our business editor believes the divorce is not likely to lessen the magnate's grip on his media empire.
Mr Murdoch, now a US citizen, reportedly paid $1.7bn in his divorce settlement from his last wife.
Ms Deng, said to be the daughter of a factory director, was born in 1968 and grew up in the eastern Chinese city of Xuzhou before leaving for the US at 19 to study.
She worked in a Chinese restaurant in California before going on to graduate from Yale University in 1996.
Ms Deng was later employed by Star TV, News Corp's Asian satellite-television operation in Hong Kong, where she met Mr Murdoch during one of his visits.
The divorce filing comes two days before News Corp is to be split into two companies, one for its entertainment assets and the other for its publishing business. Mr Murdoch is to be chairman of both firms.
His global media portfolio includes the Wall Street Journal, television channels such as Fox News and Sky, and the 20th Century Fox movie studio.
Two years ago, his UK newspaper division became embroiled in a phone-hacking scandal, which led Mr Murdoch to close one of the titles, the News of the World.
In July 2011, Ms Deng jumped from her seat during a UK parliamentary hearing to slap a prankster who tried to shove a shaving-cream pie into Mr Murdoch's face.