The Oscar winner appeared on Conan Thursday night and let show host Conan O'Brien know how he feels ISIS came about: It was former President George W. Bush and Dick Cheney's fault.
"These are the guys, [Cheney] and President Bush and some others, who invented Daesh, or ISIS," Penn said, using the Arabic name for the terror group. "I mean, they really are that which created it, and so I wanted to give him a shout-out.
"Thanks for that," he added.
He continued to slam the former vice president Cheney, referring to him as "embittered bacteria" and even questioned how the politician is even still alive, given his plaguing heart condition. "It's always a surprise to me to remember that, through bionic technology and so on, this guy's still here," he said.
Stacie McChesney; Kevin Winter/Tonight Show/Getty Images for The Tonight Show
Penn referenced politicians and advocates he admired, specifically naming Harvey Milk, a person he portrayed—and won an Oscar for—back in 2009 in the film Milk.
"We have people like Harvey Milk, who were beautiful, brilliant, impactful guys, and, you know—it's just no good deed goes unpunished, and then you've got the Cheneys. This is just me musing."
Although he was there to promote his newest film, The Gunman, Charlize Theron's boyfriend couldn't contain himself after hearing Cheney's name mentioned during the redheaded host's opening monologue. He also touched upon America's relationship with Cuba. (He has met both Fidel Castro and his brother, Raúl Castro).
"There's certainly going to be real change in Cuba," Penn said of the renewed relations between the U.S. and Cuba. "Separate and apart from the Castros, I think, as you saw, the Cuban people have incredible spirit and incredible intelligence and are very bright. Among the positive things the revolution brought are literacy. I think it's going to be a very exciting change in what they can bring to us culturally."
Penn's "as you saw" comment refers to O'Brien's recent trip to Cuba where he filmed a special episode in Havana that aired March 4.