Murdoch's Chinese-born wife gained notoriety in 2011 when she leapt to defend her husband from a pie-wielding protester. The divorce comes as News Corp is being split into independent publishing and entertainment firms.
Deng, 44, is 38 years younger than the Australian-born Murdoch.
They were married in 1999 aboard a private yacht that Murdoch had reportedly bought for his retirement, and they have two daughters, Grace and Chloe.
The news comes two days after News Corp shareholders approved a plan to split the Murdoch-led conglomerate into two independent firms.
Murdoch will remain in charge of both firms after the split.
Deng holds no formal role in the company but had been a longtime presence at her husband's side.
She met Murdoch while working at his Star Television company in Hong Kong, where former colleagues have described her as an expert networker with big ambitions.
Born in the eastern Chinese city of Xuzhou in 1968 -- at the height of the Cultural Revolution -- she left China at 19 to study in the United States. She graduated from the Yale School of Management in 1996.
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