In an opinion article in the New York Times, Clooney expressed deep affection for the US president but said personal interaction with him at a recent fundraising event in Los Angeles the Democratic party's most successful ever, raising more than $30m (£23m) - suggested Biden's stumbling performance in last month's debate in Atlanta was not an aberration.
"It's devastating to say it, but the Joe Biden I was with three weeks ago at the fundraiser was not the Joe "big F-ing deal" Biden of 2010," the longtime Democratic party member and fundraiser wrote.
"He wasn't even the Joe Biden of 2020. He was the same man we all witnessed at the debate. Was he tired? Yes. A cold? Maybe. But our party leaders need to stop telling us that 51 million people didn't see what we just saw."
More bluntly, Clooney added: "We are not going to win with this president."
Stressing that his call was made reluctantly, Clooney paid tribute to the political battles that Biden had won throughout his career but said his age represented an insurmountable adversary.
"But the one battle he cannot win is the fight against time. None of us can," he wrote.
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