Clooney, 55, was attending an event at the UN headquarters in New York as part of the UNHCR refugee summit when a CNN reporter inadvertently revealed the news, assuming he had already heard.

"All right, don't shoot me on this last question. It's a big story, you're friends with both of them. Your thoughts, any thoughts?" the reporter asked.

"What's that?"

After it became apparent that Clooney had no idea what had happened to his Oceans Eleven co-star, the reporter dropped the news: "Divorce. She filed."

"I didn't know that," a stammering Clooney replied. "That's... wow. I feel very sorry [for them], then."

Noticeably taken off guard, the actor added that it was the first he had heard of the divorce.

"That's a sad story, then. That's unfortunate for a family... That's an unfortunate story about a family. I feel very sorry to hear that."

Clooney and Pitt are long-time friends.

In March, Clooney revealed the pair were in the thick of a "prank war", saying he had purchased a special gift for Pitt after he started driving a Toyota Prius.

"I got a bumper sticker in the shape of a pot plant, that said, 'Fuck cops,' and I put that on the back of his car," Clooney said onstage at the Adobe Summit. "Because there's no way you're not getting arrested with that."

Brad Pitt and Angelina Jolie announced their separation on Tuesday night, after TMZ obtained court documents which showed she had filed for divorce from Pitt after a 12-year romance.

The couple married in 2014 in front of their six children.

The Oscar-winning actress filed in Los Angeles Superior Court on Monday, citing irreconcilable differences, court documents showed.

Jolie sought full physical custody of their six children aged eight to 15 with visitation rights for Pitt but did not seek spousal support.

"I am very saddened by this but what matters most now is the wellbeing of our kids," Pitt said in a statement to People magazine.

"I kindly ask the press to give them the space they deserve during this challenging time."

Jolie and Pitt, known collectively as "Brangelina", were one of the entertainment world's most visible couples, due to their good looks, successful films and activism.

Jolie, 41, who won a best-supporting actress Oscar for Girl, Interrupted in 2000, was previously married to actors Jonny Lee Miller and Billy Bob Thornton.

Pitt, 52, was married to Aniston in 2003 when he and Jolie began filming Mr & Mrs Smith, the story of assassins unknowingly assigned to kill each other.

Hollywood entertainment website TMZ, citing a legal filing, said Jolie "was extremely upset" by Pitt's parenting methods.

Media commentators reacted to the news with surprise and sadness.

"Today shall go down as the day love died," Vogue said in an online report on the couple's split.