James Murdoch, whose older brother Lachlan Murdoch serves as the CEO of Fox Corporation, had already left that side of the family business, partly due to his disgust of Fox News.
But he had remained on the board of News Corp — something that had intrigued friends of the family.
The younger Murdoch repeatedly clashed with his father and brother's conservative political views, occasionally even in public.
He donated to Democratic presidential candidate Pete Buttigieg and fumed about climate change denialism.
By staying on the board of News Corp, he was "testing the proposition of making change from the inside," an insider said in an interview earlier this year.
Friday's move indicates that he has given up on that proposition.
The News Corp umbrella includes papers such as The Wall Street Journal and New York Post.
It also includes the book publisher HarperCollins and a raft of newspapers in the United Kingdom and Australia.
A spokesperson for James Murdoch had no further comment and said that the letter spoke for itself.
In a joint statement, his father Rupert Murdoch and brother Lachlan said, "We're grateful to James for his many years of service to the company.
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