O'Reilly has been in hot water with the Fox News Channel in recent weeks, after numerous allegations of sexual harassment were reported in the press.
O'Reilly's exit, which was first reported by NY magazine, follows that of former Fox News Chairman Roger Ailes, who was forced to resign in July after being accused of sexual misconduct by a number of women, including former anchor Gretchen Carlson.
Those are two of the outstanding questions now that Fox News has canceled "The O'Reilly Factor".
O'Reilly said he was proud of what he termed "one of the most successful news programs in history", thanked his viewers and wished "only the best" for Fox News, the premier right-wing news outlet.
O'Reilly's attorney, Marc Kasowitz, charged that his client was being subjected to a "brutal campaign of character assassination" and that there is a smear campaign orchestrated by far-left organizations bent on destroying O'Reilly for political and financial reasons.
Southland attorney Lisa Bloom, who represents three women accusing O'Reilly of sexual harassment, called the announcement by Fox News a victory for victims who were fearless enough to come forward - and hopes more will now do the same.
Off-camera unseen forces raged against him, culminating in Fox News Channel's admission today that O'Reilly is getting the boot. One look at the O'Reilly controversy shows how it's clear that no one, including a massive news network, wants to be associated with an individual accused of sexual misconduct, even if he is steadfast in his denial.
But after The New York Times report, advertisers including BMW of North America, Allstate Corp, French pharmaceuticals maker Sanofi SA and T Rowe Price, pulled their advertising from O'Reilly's primetime show. Carlson, a veteran who has hosted shows on CNN, MSNBC and PBS, had taken over for Megyn Kelly in January when she announced she was moving to NBC News.
Jane Hall, a journalism professor at American University in Washington and former Fox News contributor called it a "significant moment" in dealing with allegations of sexual harassment, both at Fox News and in general.
Dana Perino, who had been subbing for O'Reilly who had been on vacation for the past few days, acknowledged his departure at the top of "The Factor". With a profit center gone, 21st Century Fox stock fell nearly 1 percent Wednesday in heavy trading.
A source close to O'Reilly said the broadcaster has not given much thought to his Fox-less future yet.
"I'd love to talk to him", Newsmax CEO Christopher Ruddy told CNNMoney Wednesday afternoon. Ousting O'Reilly, he said, "does not speak to a changed culture".
The National Geographic channel has aired a series of adaptations of O'Reilly books, including "Killing Reagan" and "Killing Kennedy".
Pope Francis shakes hands with TV host Bill O'Reilly, second from right, during his weekly general audience, at the Vatican, Wednesday, April 19, 2017.
In the wake of the Times report, two more women have come forward to accuse O'Reilly of harassment, one anonymously.