He made his first appearance on the show in "Osama bin Laden Has Farty Pants," when The Boys go to Afghanistan, in order to return a goat given to them by Afghan children. The Boys are later taken by terrorists who tie them up as hostages before Osama bin Laden was introduced, recording a video threatening to kill the kids and goat. U. S. soldiers, believing the goat is Stevie Nicks, engage in a battle with al-Qaeda at Osama's hideout. The Afghan boys free our boys, but leave Cartman behind, insisting he knows how to deal with him. The two go through a long routine inspired by Warner Bros. shorts produced during World War II, Cartman humiliating him in several cartoonish ways, later leaving him dazed and defeated. A soldier then executes him.
Despite his apparent death in the previous episode, bin Laden reappeared in "Krazy Kripples" as a member of the Legion of Doom, but he does not have any lines. In the Cartoon Wars duology, bin Laden reappears using live-action footage from then-recently released videos, using subtitles to change his dialogue. He threatened great harm to America if Family Guy showed the holy Muslim prophet Muhammad, but ultimately after the prophet is shown, bin Laden and al-Qaeda respond only with a video of Americans, President Bush and Jesus crapping on each other.
He later reappears as part of a class-action lawsuit against the town of South Park in "200" with other celebrities, though he does not talk. Not long after, he reappeared once more with a new, cleaned-up design in "It's a Jersey Thing". Randy Marsh sends him a video asking for help in defeating the Jerseys, playing the theme song for the show Jersey Shore to bin Laden. After South Park runs out of ammo, he responds with several al-Qaeda suicide bombers who destroy the Jerseyites. Jersey pushed back, the entire town honors bin Laden - before a U.S. soldier takes him out, causing Randy to proclaim "We got him!"
Just seven months after being shot in the head by a Paratrooper in "It's a Jersey Thing," Osama bin Laden was found and killed by U.S. Navy SEALs in Pakistan through a shot to the head on May 1, 2011. In another parallel, Randy's response in "It's a Jersey Thing" is identical to that given by Barack Obama ("We got him!"). "Funnybot" and "Royal Pudding" include many subtle references, including a sketch in Funnybot's writing room and Obama's speeches (though about Funnybot and later Tyler Perry) and in the latter, the response to Tooth Decay's death.
Osama wore a white taqiyah, an oversized white robe, and a light gray shirt. He also had comically oversized ears, as well as an oversized nose, oversized lips, and small eyes.
Osama was a terrorist, meaning that he was willing to use violence for personal gain.
- Despite being against the use of Muhammad on Family Guy, he was among the celebrities planning to take his power of not being able to be made fun of in "200" and "201."
- Osama, along with all the other terrorists in South Park, never spoke in an actual foreign language. He was supposed to be speaking Arabic, but all his dialogue was only consisted of the words Muhammad, jihad, and gibberish including the word "derka." The dialogue was similar to the "Arabic" in Team America: World Police, a movie by Trey Parker and Matt Stone.