"After a thorough and careful review of the allegations, the company and Bill O'Reilly have agreed that Bill O'Reilly will not be returning to the Fox News Channel," 21st Century Fox said in a statement.
The star host has been dogged by misconduct claims — some sexual in nature — since an April 1 story in The New York Times detailed alleged settlements made between the host and five women who accused him of harassment and sexual misconduct.
An internal 21st Century Fox memo obtained by ABC News said that the "decision follows an extensive review done in collaboration with outside counsel." The memo was signed by Rupert, Lachlan and James Murdoch, the company's top executives.
"We want to underscore our consistent commitment to fostering a work environment built on the values of trust and respect," the memo concluded.
Commenting on the news, O'Reilly said, "It is tremendously disheartening that we part ways due to completely unfounded claims. But that is the unfortunate reality many of us in the public eye must live with today."
Earlier in April, 21st Century Fox enlisted the prominent law firm Paul, Weiss, Rifkind, Wharton & Garrison to probe at least one complaint against O'Reilly.
"21st Century Fox investigates all complaints, and we have asked the law firm Paul, Weiss to continue assisting the company in these serious matters," a 21st Century Fox spokesman said at the time.
Scores of advertisers pulled their spots from his top-rated show, "The O'Reilly Factor," in the days after the publication of the Times story. ABC News has not been able to independently verify the claims made in it.
In the internal memo, the Murdochs praised O'Reilly, saying, "By ratings standards, Bill O'Reilly is one of the most accomplished TV personalities in the history of cable news. In fact, his success by any measure is indisputable."
Kantar Media, a market research firm, said in early April that "The O'Reilly Factor" pulled in more revenue than any other show on Fox News or its main competitors CNN and MSNBC. In 2015, "The Factor" brought in some $126 million, Kantar said.
Fox News Channel released a statement today announcing its new prime-time lineup in the wake of O'Reilly's departure.
Among other changes, recently hired host Tucker Carlson will get O'Reilly's 8 p.m. ET time slot starting on Monday, the network said. For the remainder of this week, O'Reilly's show will continue with guest hosts.
On Wednesday's show, guest host Dana Perino addressed O'Reilly's departure at the start of the show, saying, "Before we get to the other big stories of the day, we want to address the situation many of you may already be aware of. Bill O'Reilly, who hosted this program for 20 years is leaving the Fox News Channel. We know that you, his very loyal viewers, will have a lot of feelings about this."
And at the close of the show Perino continued, "It is the end of an era here at the Fox News Channel ... Bill has been the undisputed king of cable news, and for good reason. He is an incredibly talented broadcaster who raise the bar for interviewers everywhere. He has also held the staff to exacting standards in his quest to put the best possible program on the air and they are great. And you, his audience, responded in record numbers making 'The Factor' the number one cable news show for more than 16 years. You have also been loyal and we can’t tell you how much that means to everyone on 'The Factor.'"
And the logo for the show was noticeably different Wednesday: Instead of "The O'Reilly Factor," the logo read "The Factor."
Pressure on O'Reilly increased again this week with a report in New York magazine on Tuesday that claimed — citing three unnamed sources — that the Murdoch family, which controls 21st Century Fox, was "leaning toward announcing that O'Reilly will not return to the air."
The same day, The Hollywood Reporter published a story saying another woman had come forward to make misconduct allegations against O'Reilly.
Celebrity attorney Lisa Bloom, who is representing the woman in the Hollywood Reporter story as well as an accuser featured in the Times story, appeared Wednesday on ABC News' "Good Morning America." Bloom said that her client, an African-American woman, is alleging that O'Reilly called her "hot chocolate."
Bloom said that she and her clients were "not going to stop until Bill O'Reilly is fired."
After the Times investigation, O'Reilly wrote on his website that "like other prominent and controversial people," he is "vulnerable to lawsuits from individuals who want me to pay them to avoid negative publicity."
He also wrote that he is "a father who cares deeply for my children and who would do anything to avoid hurting them in any way" and therefore had to "put to rest any controversies to spare my children."
Not even a vote of confidence from the president could save O'Reilly's job.
O'Reilly is not the first high-ranking Fox News employee to exit the network amid sexual misconduct claims.
Ailes has denied wrongdoing.
ABC News' Michael DelMoro, Santina Leuci, Rebecca Jarvis, Aaron Katersky, Josh Margolin and Joshua Hoyos contributed to this report.