According to the publication's bombshell report, the royal pair's blowout erupted following 71-year-old Camilla's return home from royal engagements.
Charles was blindsided by the news, GLOBE claims.
GLOBE adds that Camilla's previous blowouts with the Royal Family were partly to blame for the new split.
"The royals are convinced Camilla is nuts!" a source says.
"She's been fighting the entire family," the insider adds.
Since telling Prince Charles the news, GLOBE reports Camilla is on the warpath.
"She's threatened to reveal all the royal family's darkest secrets."
Camilla is demanding a "$400 million payout" to keep quiet, the US publication reports.
"There are frantic talks going on behind closed doors at Buckingham Palace, trying to negotiate some sort of face-saving compromise."
"But, you know Camilla will play hardball.
"There's nothing worse than a wannabe queen scorned, and the royals are bracing for one of the nastiest - and most expensive - royal bust ups in history."
The Royal Family is yet to respond to GLOBE's claims.