Mr. Bill got its start when Walter Williams sent Saturday Night Live a Super-8 reel featuring the character in response to the show's request for home movies during the first season. Mr. Bill's first appearance occurred on the February 28, 1976 episode. Williams became a full-time writer for the show in 1978, writing more than 20 sketches based on Mr. Bill.
Each Mr. Bill episode would start innocently enough but would quickly turn dangerous for Mr. Bill. Along with his dog, Spot, he would suffer various indignities inflicted by "Mr. Hands," a man seen only as a pair of hands (played by Vance DeGeneres). Sometimes the abuse would ostensibly come from the mean Sluggo, another clay character. (However, Mr. Hands did most of the violence himself, because Sluggo would tell him to, i.e. "Sluggo says to...") The violence would inevitably escalate, generally ending with Mr. Bill being crushed or dismembered while squealing in a high pitched voice, "Ohhhh noooooooooooooo..." The character's popularity spawned the 1986 live-action movie Mr. Bill's Real Life Adventures.
- Mr. Bill - The Main Clown Star of the show. His catchphrase is "Oh, No!!!"
- Spot - Mr. Bill's dog, who died in most episodes.
- Sluggo - The Main clay Villain. However, Mr. Hands did most of the violence himself, because Sluggo would tell him to, i.e. "Sluggo says to..."
- Mr. Hands - The man seen only as a pair of hands (played by Vance DeGeneres). He does most of the violence himself, because Sluggo would tell him to, i.e. "Sluggo says to...")
- Miss Sally
- Mr. Bill's Mom
- Sluggo Clones
- In the 1980s, Mr. Bill was featured in advertising spots for Pringles Butter and Herb flavored Potato Chips, where he gets run over by a can of Pringles and says "oh no". In 1988, Mr. Bill also appeared in a series of anti-drug announcements which showed him engaging in various activities such as basketball until Sluggo would bury him under a bunch of pills, in which the tagline would be "Say OH NO! to drugs".
- Mr. Bill also made a brief cameo appearance during the 1981 "Get High On Yourself" NBC-TV anti-drug campaign. Mr. Hands suggests to Mr. Bill that he try getting high on himself. Mr. Bill agrees, and the camera pulls back to reveal that Mr. Bill is lashed to the exterior of a NASA Space Shuttle. As it lifts off, he cries "Oh noooooo..."
- Mr. Bill was the answer to a puzzle on Password Plus in 1981. Host Tom Kennedy, panelist Dick Martin, and a member of the NBC studio audience took part in a Mr. Bill skit.
- In the 1990s, Williams created a series of Mr. Bill-like advertising spots for Pizza Hut, featuring "Pizza Head" in the usual Mr. Bill role and a pizza cutter named "Steve" in the Sluggo role.
- With Comedy Central producing many "We're all going to die" promos in the early 1990s, Mr. Bill starred in one of them, featuring him in a makeup room explaining how making movies can be dangerous, but the real world can be more dangerous, so he reminds us to always be careful. Mr. Hands tells Mr. Bill they need him on the set and has to blow dry his hair, resulting in Mr. Bill's entire face melting.
- Mr. Bill appeared in a Burger King commercial where Mr. Hands tells Mr. Bill that Burger King changed their Whopper. Mr. Bill was upset about the loss of his favorite burger, but Mr. Hands tells him that the new Whopper was bigger than McDonald's Big Mac or Wendy's Single. Mr. Hands sends Mr. Bill into the restaurant and gives him one. Mr Bill loves the Whopper and asks for another one. Mr. Hands agrees but he says it's on him and drops the Whopper box onto Mr. Bill, crushing him.
- Children's television network Nickelodeon adopted a Mr. Bill like mascot named Stick Stickly, a talking popsicle stick, as the host for their "Nick in the Afternoon" block.
- In 1998, Mr. Bill was given his first television series in nearly 20 years, which was titled Ohh Nooo! Mr. Bill Presents and aired on the Fox Family Channel. As well as featuring typical Mr. Bill-type sketches, other sketches, most notably ones from British personality Mr. Bean, were present in the one-hour variety show. It lasted forty episodes.
- In 2004, Mr. Bill was part of a campaign aimed at teaching people, especially children, about the loss of Louisiana's coastal marshes and swamps. On May 27, 2004 CNN showed a segment with Mr. Bill being 'evacuated' from a New Orleans roof the year before Katrina. "Mr. Bill: Hurricane Sluggo".
- In early December 2008, Mr. Bill became one of Subway's spokesmen, along with Mr. Hands. In the commercial, Mr. Bill learns how to make bread with Mr. Hands, but suddenly Chef Sluggo comes in to roll the dough. But Sluggo never gets a chance to hurt Mr. Bill, as a boulder comes and crushes the whole Subway restaurant with both characters inside. When Mr. Hands finds Mr. Bill flattened with the dough on the side of the boulder, he says, "Great idea, Mr. Bill! Flatbread!"
- MasterCard has enlisted Mr. Bill for one of its "Priceless" ads, which officially began airing on June 9, 2008. It is interesting to note that the commercial was noticeably nicer to Mr. Bill. Although he was thrown around as he usually is, he isn't crushed as in the SNL sketches. The commercial starts with Mr. Bill being served coffee by Mr. Hands (coffee: $2). Mr. Hands fills the cup too much causing the coffee to spill all over the floor and Mr. Bill, but Mr. Bill takes it with good nature, saying, "I always wanted brown shoes. Yay!" Next, Mr. Hands tells Mr. Bill at a gym, "Your fitness instructor says to take it up a notch. [gym membership: $59]" He turns the treadmill all the way up and drops Mr. Bill on it, causing him to fly across the gym. Luckily, Mr. Bill lands safely on a stationary bike, where he says, "Hey! There's a bike open!" Next, Mr. Bill is seen in his luxurious office, where Mr. Hands helps him unpack his suitcase (suitcase: $120). When the suitcase opens, it knocks into Mr. Bill, sending him flying out the window. He lands on the windshield of a bus, where he remarks, "Hey, the bus is right on schedule!" He is then knocked off the bus by its windshield wipers as the commercial ends (Getting through the day: Priceless).
- The March 29, 2010 episode of Jeopardy! featured a category called "Mr. Bill Does the Bard". The category featured the character portraying various Shakespearian characters in CGI vignettes, who, like the sketches, all met their untimely demise.
- On September 23, 2010, official Mr. Bill iPhone game was launched on Apple's AppStore by Capcom.
- The October 22, 2010 episode of the CBS drama Medium, featured Mr. Bill being abused by the show's principal character Allison Dubois during the opening dream sequence while being filmed in the style of the SNL skit.
- In 2011, Mr. Bill was in a commercial for Wonderful Pistachios.
- "Oh Noooooo! It's Mr. Bill's 20th Anniversary (1995)". Internet Movie Database. Retrieved 2008-06-04.
- Lee, Wendy A. (June 3, 2008). "Mr. Bill Returns (in One Piece) to Pitch a Debit Card". New York Times. Retrieved 2008-06-04.