"You do need a new sheriff," the Real Time host said on his show on Friday night.
"This is well within what satire has always been."
Maher supported Musk in turning Twitter into a "town square" of thoughts and opinions instead of a "left wing place." The comedian announced that Twitter was a place for people who want their news to reflect their politics.
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Maher then took aim at President Barack Obama's idea that Generation Z would figure out how to fight misinformation was way wrong.
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"I'd much rather have Elon Musk making the rules that a 23-year-old who can't take the joke on Babylon Beeswax, or whatever the f*** that is," he stated.
"I mean, this is a generation that doesn't know what the word 'violence' means. They think 'violence' means 'anything I don't like.' Their standard of free speech is 'I'm uncomfortable.' That's not where the standard is, right?"
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Maher, 66, brought up the takeover twice throughout his April 29 show that airs on HBO.
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The first was throughout his monologue, and the topic came up once more during the panel discussion with former Alabama Senator Doug Jones, New York Times writer David Leonhardt and MSNBC host Ali Velshi.
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In April, it was declared that Musk, the founder of Tesla and SpaceX, obtained Twitter in a $44 billion leveraged buyout.
In his monologue at the top of the show, Maher laughed that one of Musk's commitments was to get rid of bots on Twitter. He quipped that Facebook CEO Mark Zuckerberg replied to that promise, "Why are you making it personal?"
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Earlier this week, Musk tweeted that his next plan was to purchase Coca-Cola and have the company start using cocaine as an ingredient again. Maher jokes, "Sure, it's all fun and games, until Hunter Biden gets his head stuck in the vending machine."
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Maher told his guests later in the show that Twitter has "failed" being a judge over what can and cannot be announced in public discourse.
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He went on, "You failed when you threw the New York Post off of Twitter for talking about Hunter Biden's emails. And it turned out to be a real story. You failed when you said we couldn't read about whether COVID had come from a lab. You failed!"
Shifting his attention to conservative satire site The Babylon Bee, Maher denounced Twitter employees for flagging a video that blamed them for being too sensitive.
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