Sheen was famously fired from his sitcom "Two and a Half Men" in March after a very public meltdown during which he claimed to be a "rock star from Mars" who has "tiger blood" and "Adonis DNA."
The 46-year-old actor is the subject of the latest roast, which was taped Saturday night at Sony Studios and will air Sept. 19 on Comedy Central.
Sheen took the stage in true rock-star fashion, as rock `n' roll guitarist Slash heralded his introduction. The actor, dressed in a black suit, white shirt and red tie, smiled and laughed as roasters jabbed at his famous family, his notorious taste for drugs and prostitutes and his primetime firing.
"Charlie's meltdown was so bad, Al Gore's making a documentary about it," quipped comedian Jeffrey Ross, who was dressed as Muammar Gaddafi in a military outfit with fringed epaulets and a sash.
"The only time your kids get to see you is in re-runs," Ross said.
Comedian Jon Lovitz also took a timely swipe at Sheen: "How much (cocaine) can Charlie Sheen do?" he asked. "Enough to kill two and a half men."
Priceline pitchman Shatner reminded Sheen to "book your next rehab stay through Priceline.com."
Walsh, who is best known for her roles on "Grey's Anatomy" and "Private Practice," gave standup a shot at the roast. "It's amazing, despite all those years of abusing your lungs, your kidneys and your liver, the only thing you've had removed is your kids," she said to Sheen.
The most bizarre performer was Tyson, who got plenty of laughs despite his almost unintelligible delivery. "I'm the greatest poet alive," he said as he concluded his time on stage. "I will eat your children!"
Comedian Amy Schumer joked, "Is his interpreter here?"
Steve-O of "Jackass" fame was also among the roasters. His big trick was running repeatedly into Tyson's fist, which he did until he reportedly broke his nose.
The comics also took digs at Sheen's former live-in girlfriends, whom he referred to as "the goddesses," and ex-wife Brooke Mueller, who was sitting in the audience Saturday.
After the comedians had their say, roast master Seth MacFarlane introduced the night's honoree as "a man with a big heart, because it's been dangerously enlarged by cocaine use."
Sheen jabbed back at his roasters and poked fun at his image.
"It's true I've hung around with a lot of shady people over the years: Losers, drug addicts, dealers, desperate whores," he said. "But to have you all here on one night is really special."
He sipped a drink as he addressed the crowd, who sat in bleachers and at bar tables inside Sony Studios' stage 27. At one point, he seemed to reflect sincerely on his career, talking about how he had "the biggest salary on television" and publicly enjoyed drugs and porn stars before telling off his boss.
"And then it was gone in one fiery public flameout," he said.
"It was only when the smoke cleared I realized just how lucky I am, because even after all that, I still have a family that loves me. That's why they're not here tonight," he continued. "They've seen me in jail. They've seen me rushed to emergency rooms. They've seen me dragged into court. But seeing me on basic cable would kill them."
He said he's done with his catchphrase -- winning! -- because he feels he's already won.
"This roast may be over, but I'm Charlie Sheen, and in here burns an internal fire," he said, touching his chest. "I just have to remember to keep it away from a crack pipe."