Presenter Bill O'Reilly has been dropped from Fox News over sexual harassment claims, the company says.
"After a thorough and careful review of the allegations... Bill O'Reilly will not be returning," the network said in a one-sentence statement.
He has been on holiday since 12 April, and was seen shaking hands with Pope Francis at the Vatican on Wednesday.
O'Reilly said it was "tremendously disheartening" to leave over "completely unfounded claims".
More than 50 sponsors have withdrawn ads from his show, The O'Reilly Factor.
Pressure on Fox has mounted since recent reports that five women had received $13m (£10m) in payouts because of O'Reilly's behaviour.
The prime-time presenter, who has been with the US network almost since its inception, has denied all of the allegations.
"It is tremendously disheartening that we part ways due to completely unfounded claims," he said in a statement released after his dismissal.
"But that is the unfortunate reality many of us in the public eye must live with today."
Fox broadcaster Tucker Carlson will be taking over Mr O'Reilly's slot, the company said in a follow-up statement.
In an internal memo sent to 21st Century Fox employees, the company wrote that the decision had been made after "extensive review done in collaboration with outside counsel".
The letter - signed by Rupert Murdoch and his sons Lachlan and James - praised Mr O'Reilly as "one of the the most accomplished TV personalities in the history of cable news".
It added that the network was committed to "fostering a work environment built on the values of trust and respect".
Analysis: Anthony Zurcher, BBC News, Washington
The sexual harassment charges against Bill O'Reilly aren't new. They've bubbled up before and have been quietly ushered from view, thanks to multimillion-dollar legal settlements.
Now, however, they have brought down the top-rated conservative talk show on cable news.
So what changed? Was it lurid details of his alleged behaviour? The protests? Commercial sponsors abandoning his show? The impact the scandal could have on 21st Century Fox's attempts to purchase European broadcaster Sky?
All probably contributed to O'Reilly's exit. The crack in the proverbial dam, however, came when Fox News head Roger Ailes was sacked for his own sexual harassment scandal.
If Mr Ailes, who built the conservative television empire, could be laid low by his tawdry behaviour, no one was untouchable - even Mr O'Reilly.
Welcome to Fox News in the Donald Trump era. Mr Ailes is out. Mr O'Reilly is gone.
Presenter Megyn Kelly has bolted to NBC. The only giant left standing is Trump super-fan Sean Hannity.
A network that defined itself by blanket opposition to Barack Obama now appears adrift, challenged by more aggressive conservative media outlets and toxic to the left.
It's a tricky position to occupy - a victim of its own success… and hubris.
The O'Reilly Factor drew nearly four million viewers per night.
The most recent allegation came on Tuesday evening when lawyer for a former African-American clerical worker at Fox alleged her client had been harassed by Mr O'Reilly in 2008.
Lawyer Lisa Bloom said the Fox News host had referred to the unidentified woman as "hot chocolate".
"He would leer at her," said Ms Bloom. "He would always do this when no-one else was around, and she was scared."
Media-watchers say the allegations had become too much of a liability for 21st Century Fox.
A concern for the Murdoch family is their pending $14bn (£11bn) deal to buy out satellite provider Sky, which is being scrutinised by British regulators.
Earlier this month authorities with the European Commission cleared 21st Century Fox to acquire the remaining 61% of Sky that it does not yet own.
Sources at the company tell US media that Rupert Murdoch was in favour of keeping Mr O'Reilly in his post.
But James Murdoch, chief executive officer of 21st Century Fox, reportedly argued that Mr O'Reilly should go.
The company reputation has taken a hit after sexual harassment allegations were also levelled at Roger Ailes, the former head of Fox News.
Mr Ailes resigned in 2016 after being sued by a former Fox News presenter, Gretchen Carlson.