The news was first reported by Deadline Hollywood, which covers the entertainment industry. A spokeswoman confirmed the divorce filing to The New York Times and said the "relationship between husband and wife has broken down irretrievably."
Unnamed analysts told Deadline Hollywood they do not expect the divorce to have any effect on Murdoch's global media empire.
Murdoch, 82, has one daughter from his first marriage and two sons and a daughter from his second, to Anna Torv Murdoch, which lasted 31 years. He and his third wife, who is 44, have two daughters.
Wendi Deng Murdoch, who was born in China and attended college in the United States, met Murdoch while she was working for his Star TV operation in Hong Kong and married him on a yacht in New York Harbor in 1999.
Murdoch's News Corp. announced this week it is splitting into two entities.
Murdoch angered his wife in 2006 when he said in an interview with Charlie Rose his daughters with Wendi would not have the same voting rights in his company as his other children. While rumors about the couple's relationship have been persistent, video of Wendi Murdoch trying to protect her husband from a pie-thrower last year in London while he testified on the hacking scandal went viral on the Internet.