- "We're entering an entirely new era," says Michael Wolff, author of "The Man Who Owns the News."
- Under scrutiny for the handling of sexual harassment scandals, co-president Bill Shine resigns.
- The departures of Bill O'Reilly and Megyn Kelly took Fox's "unique chemistry" with its viewers with them, Wolff says.
Fox News Channel, as it's been known to cable viewers for more than two decades, is done for, Rupert Murdoch biographer Michael Wolff told CNBC on Tuesday.
Under scrutiny for the handling of several sexual harassment scandals against former host Bill O'Reilly and then-CEO Roger Ailes, Bill Shine resigned Monday as co-president. Shine has not been accused directly, but lawsuits have blamed him for a workplace culture in which sexual harassment developed.
"Fox is finished. Fox that we have known for 20 years is over," Wolff said on "Squawk Box." "This represents kind of a cable
O'Reilly agreed to leave Fox News in April, nine months after Ailes was forced out. O'Reilly and Ailes deny the claims.
Fox News host Megyn Kelly, who accused Ailes of unwanted sexual advances, left the network in January and is now with NBC News.
Wolff, a Hollywood Reporter columnist, said the "unique chemistry" O'Reilly and Kelly had with their devoted prime-time audiences cannot be replicated.
"All that chemistry is gone because all those people are gone," said Wolff, whose 2008 book "The Man Who Owns the News: Inside the Secret World of Rupert Murdoch" is a biography of 21st Century Fox's executive chairman.
Ahead of Shine's resignation, conservative commentator Sean Hannity expressed support on Twitter for Shine with the hashtag #Istandwithbill.
Shine was at Fox News from the start, originally coming in as Hannity's producer in 1996.
"We will definitely lose Sean Hannity, if not in days in months," Wolff predicted.
The ratings have held up pretty well at Fox News since it was forced to shake up its prime-time lineup last month.
Tucker Carlson replaced Kelly at 8 p.m. ET and the popular ensemble show, "The Five," replaced O'Reilly at 9 p.m. ET.
Hannity stayed at 10 p.m. ET.
But Wolff thinks an O'Reilly-less lineup is "completely not sustainable," calling the troubles at Fox News "a wide open opportunity" for rivals who want to reach a right-leaning audience.
"All those ratings happened because [of] O'Reilly at 8 o'clock. You just have a fall off of his audience across the night. ... Now you start with a lower baseline," Wolff said. "We are just left with a network that has a significant penetration but no reason for people now to really watch it."
Wolff said the decisions to part ways with Shine, O'Reilly, and Ailes were driven by Murdoch's sons.
James Murdoch is CEO of 21st Century Fox and older brother Lachlan is executive chairman.
"It is the decision the Murdoch sons wanted," Wolff said. "They don't want it tainted by Murdoch politics and ideology."
"I think it's the wrong decision from a shareholders' position," Wolff added. "This is going to cost them an enormous amount of money."
Fox did not immediately respond to CNBC's request for comment.
— Disclosure: NBC and CNBC are owned by Comcast's NBCUniversal unit.