"Really? I don't think so," Griffin told host Carrie Bickmore on The Project.
"I'm not in the movie business, and I knew... I can't imagine that those guys didn't know," she said.
Damon in particular came under fire this week for new comments where he defended his repeated work with Weinstein, despite ongoing rumours of his harassment and abuse.
"People say, 'everybody knew', like, yeah I knew," Damon told ABC News.
"I knew he was an asshole - he was proud of that. I knew he was a womaniser - I wouldn't want to be married to the guy. But the criminal sexual predation is not something that I ever thought was going on. Absolutely not," he said.
On The Project, Griffin said while she'd never been harassed by Weinstein, she recalled an uncomfortable meeting with the disgraced movie mogul at, of all places, a comedy roast of friend Quentin Tarantino (Tarantino last week said he wished he'd "done more" to stop the producer's actions).
"I sat next to Harvey Weinstein... I'm not hot enough for him to sexually assault. That's his mind set," she joked.
"I remember him saying to me, bragging about the wife who worked for Balenciaga, 'Maybe my wife could dress you some time for the Emmys.'
"I remember thinking, 'I wonder if that's one of the ways he would ensnare young actresses...' And then an article came out saying that was one of his tools: 'My wife works for Balenciaga, come to my room, we'll fit you for a gown'," she said.
The outspoken comedian had Ten's producers sweating, after she levelled accusations at other powerful men in Hollywood.
"This is an epidemic," she told the panel.
" ... All the network and studio heads, they all have to go down.
"Harvey Weinstein, he's not one single case. But the white middle-aged guys and older guys that are running every network and studio in the United States, they all behave this way and everyone covers for them," she said.
Griffin, who says she's been blacklisted by US media following her notorious 'beheaded Trump' stunt, also went hard on her recent run-ins with the US president.
"I'm gonna call him a moron - and a Nazi," she joked. "Americans are skittish of calling him a Nazi, but he's a Nazi. There's a Nazi in the Oval Office, so heads up!"
She revealed that, in the earlier days of their acquaintance, Trump once scammed her into hosting a charity gig.
"Of course I found out later he didn't give any of the money to charity," she said.
"He's just a big liar and awful and everybody should get rid of him soon. I don't mean violently!" she added with a wink. "I mean vote him out."
In an awkward bit of legal covering, Bickmore was later forced to throw in the disclaimer that "all of Kathy's views on the show tonight are her own".
"A little voice in my ear just told me to say that," Bickmore laughed.
Griffin is currently on a stand-up tour of Australia, with gigs in Melbourne and Perth remaining.
The story Kathy Griffin calls out Hollywood's harassment 'epidemic' first appeared on The Sydney Morning Herald.