Speaking on Wednesday at the Venice Film Festival, where received a Golden Lion for Lifetime Achievement, the actor, filmmaker and political activist said deepfake technology and AI-generated content were undermining trust in information.
"It's getting harder and harder for us to discern the truth," Clooney told reporters, adding that the burgeoning technology could make people doubt genuine evidence.
"Worse than that, because you poison the well of saying 'maybe this is true', 'maybe this isn't', then when you see real things that are really true, people are able to say, 'Well, that's fake'," he said.
The two-time Oscar winner, who has won awards for his campaigns to promote justice, said he recently met leading AI developers and was unconvinced current safeguards would be enough to keep pace with improvements in the technology.
"Everybody's working furiously at it, and I haven't seen any great strides yet in success," he said, joking that he didn't want to think of his likeness being used after he has gone.
"I would like to avoid being in a tampon commercial 20 years after I'm dead," he said.
He linked the AI challenge to wider concerns about journalism, saying media ownership had become concentrated in the hands of a small number of wealthy individuals.
"The richest people in the world right now are owning the Washington Post and Twitter and most of the places we get our information, and that is a concern," he said, referring to Jeff Bezos and Elon Musk respectively.
"The state of journalism is always in flux, always challenged," he said.
"But I do believe that information will find its way out."
Clooney was in Venice to receive the festival's top career honour after nearly three decades of regular appearances on the Lido, dating back to the premiere of Out of Sight in 1998.
Reflecting on receiving the award at 65, Clooney joked that growing older inevitably brought a touch of melancholy.
"Everything is melancholy," he said.
"You brush your teeth and think, 'My teeth used to be so much nicer.'"
