Murdoch filed a one-page document Thursday indicating that he was opening a divorce case in New York State Supreme Court in Manhattan.
A News Corp. spokesperson confirmed the filing.
A sealed document with the filing says, "the relationship between the husband and wife has broken down irretrievably," according to a person familiar with the matter, who spoke on condition of anonymity because the matter was personal.
The couple are parents to two daughters, Grace and Chloe, ages 11 and 9. The girls have no voting stake in the company, but they are beneficiaries of 8.7 million non-voting shares that are held in a trust. Wendi Deng Murdoch, 44, also has non-voting shares.
Murdoch controls nearly 40 percent of the voting shares of News Corp. through a separate family trust. He has four other children from two previous marriages, including three who have active roles within the company: James, Lachlan and Elisabeth.
All four children, including Prudence, his child from his first marriage, have equal votes in electing trustees. That means that upon Murdoch's death, his four eldest children will continue to have the most say in who controls News Corp.
Rupert Murdoch's lawyer, Ira Garr, did not immediately respond to a request for comment.
The divorce filing comes just a week before the company begins the process to split in two. One company will contain a publishing division and Australian TV assets. A separate company will house global TV and movie businesses.
Markets appeared to be unfazed by the announcement. After starting the day in negative territory, News Corp.'s widely traded non-voting shares were up 1.4 percent at $31.37 by late afternoon.
Born in China, Wendi Deng Murdoch is a Yale graduate who went on to work as a junior executive at News Corp.'s subsidiary Star TV in Hong Kong. Deng was introduced to Murdoch at a Hong Kong cocktail party in 1997. She left Star TV before marrying the media mogul in June 1999 aboard Murdoch's private yacht, in New York.
She produced the movie "Snow Flower and the Secret Fan," which was released in 2011 by News Corp.'s Fox Searchlight. According to entertainment website IMDb, The movie did not recoup its $6 million budget.
Wendi Deng Murdoch leapt into the spotlight during a July 2011 British parliamentary hearing into phone hacking by News Corp. newspapers. She jumped up to smack a protester who was throwing a cream pie at her husband.___
Associated Press writer Jennifer Peltz in New York contributed to this report