James Murdoch, the younger son of media mogul Rupert Murdoch, has resigned from the board of News Corporation citing "disagreements over editorial content".
In a filing to US regulators, he said he also disagreed with some "strategic decisions" made by the company.
The exact nature of the disagreements was not detailed.
But Mr Murdoch has previously criticised News Corp outlets, which include the Wall Street Journal, for climate change coverage.
In recent years James Murdoch has also found himself at odds - politically - with his father, BBC North America correspondent David Willis says.
Whilst Murdoch Senior has pledged support for Donald Trump, James Murdoch has reportedly contributed hundreds of thousands of dollars to the campaign of Mr Trump's Democratic rival, Joe Biden.
James Murdoch's departure from News Corp would, our correspondent says, appear to grant even more influence to his brother Lachlan who is generally thought to share his father's more conservative views.
Rupert, News Corp's executive chairman, and Lachlan, co-chairman, wished James well in a joint statement.
"We're grateful to James for his many years of service to the company," the statement said. "We wish him the very best in his future endeavours."
News Corp also owns The Times, The Sun and The Sunday Times in the UK, as well as a stable of Australian newspapers, including The Australian, The Daily Telegraph and The Herald Sun.
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What do we know about past disagreements?
Earlier this year, amid devastating wildfires in Australia, James Murdoch and his wife Kathryn expressed their frustration with climate change coverage by News Corp and Fox.
Their spokesperson told The Daily Beast they were "particularly disappointed with the ongoing denial among the news outlets in Australia given obvious evidence to the contrary."
Rupert Murdoch has described himself as a climate change "sceptic" and denies employing climate deniers.
But critics of News Corp pointed to its comment articles and reporting of the alleged role of arson in the wildfires as minimising the impact of a changing climate.
Who is James Murdoch?
Born in London in 1972, he is the youngest of Rupert Murdoch's three children from his marriage to Anna Torv, the others being sister Elisabeth and brother Lachlan.
He was schooled in New York, going on to study film and history at Harvard University but he dropped out in the mid-1990s without completing his degree.
Gaining a reputation as the family rebel, he set up an independent hip-hop label, Rawkus Records, which launched the career of rapper-actor Mos Def and gave an airing to the then little-known Eminem.
He was formerly chief executive of 21st Century Fox before Walt Disney bought most of its assets last year.