Wendt is a 1975 alumnus of The Second City, which he discovered shortly after college. A viewing had inspired him to join and on his first day of employment, he showed up promptly at 11:30 am as he was instructed. The woman working there handed him a broom and said "Welcome to the theater, kid"; thus, his first job in show Business was sweeping the floors. Second City was also where he met his Future wife, Bernadette Birkett, who played Cliff's Halloween date in the third season of Cheers and later in the series played the voice of Norm's never-seen wife, Vera.
Wendt appeared in the 1980 film My Bodyguard. He played a handyman working behind the check-in counter at the Ambassador East Hotel in Chicago (now the Public Hotel).
In 1981 Wendt appeared on an episode of the TV series Taxi as an exterminator and on an episode of the TV series Soap as a counterman in a diner. He starred as Private LaRoche in a 1982 episode of M*A*S*H, where he suffered from having a pool ball stuck in his mouth for much of the episode. He had an uncredited appearance in Airplane II: The Sequel as the ticketing agent who tells a woman that she can only have one carry-on bag.
From 1982 to 1993, Wendt appeared as Norm Peterson in all 275 episodes of Cheers. For his work on Cheers, Wendt earned six Primetime Emmy Award nominations for Best Supporting Actor in a Comedy Series.
His first appearance on Saturday Night Live was in a Season 11 (1985–1986) episode where he shared hosting duties with Director Francis Ford Coppola. In 1988 he played the part of "Witten" in the New Zealand-made film, Never Say Die. In the early 1990s, Wendt made cameo appearances on several episodes of SNL as Bob Swerski, one of the Chicago Superfans (along with cast members Chris Farley, Mike Myers, Robert Smigel, and one-time host, Joe Mantegna). Having grown up as a lifelong fan of his hometown Chicago White Sox and Chicago Bears, Wendt's Bob Swerski character is said to be a "spot-on" characterization of Chicago's south-side citizens.
In 1989, Wendt appeared as the eponymous protagonist in a BBC TV dramatization of Ivan Goncharov's novel Oblomov. He has also appeared twice on the original British edition of Whose Line Is It Anyway?. In 1991, Wendt played the father in Michael Jackson's music video, Black or White. In 1994 he appeared in the film Man Of The House as Chet Bronski, the stepfather of Norman (Zachary Browne), and starred with Chevy Chase, Jonathan Taylor Thomas and Farrah Fawcett. He also played the role of "Old Man Dunphy"'s closeted homosexual friend Joey in the 1999 film, Outside Providence.
Wendt starred as the killer in one of the last episodes of the TV series Columbo, portraying a thoroughbred horse owner in the 1995 episode Strange Bedfellows. Wendt appeared as himself on Seinfeld and has reprised the character Norm Peterson on The Simpsons episode "Fear of Flying", two episodes of Family Guy "Road to Rupert" and "Three Kings" as well as the Frasier episode "Cheerful Goodbyes". In the same year as his Frasier guest appearance, Wendt played the bartender to Ted Danson's character in Becker (the inverse of their relationship on Cheers). In 2003, Wendt appeared as a Celebrity Fisherman in the music video for Corba Verde's "Riot Industry" along with Rudy Ray Moore (of "Dolemite" fame) and The Minutemen's Mike Watt. He appeared in several episodes of The WB's Sabrina, The Teenage Witch in 2001 as the title character's boss. He also was the host of the A&E reality show, House of Dreams in 2004. In January 2006, Wendt was seen again on television screens as part of the cast of Modern Men.
He has also appeared on The Larry Sanders Show as a guest on the show. In May 2006, Wendt was seen yet again on television. He made several appearances on Late Night with Conan O'Brien where he performed short skits. His appearance on Late Night was in all likelihood because the show was having a week-long event in his home town of Chicago. He starred in a 2006 episode of Masters of Horror entitled "Family", directed by John Landis and played Santa Claus in the ABC Family original film Santa Baby. Wendt performed alongside Richard Thomas in Twelve Angry Men in October 2006 in the Eisenhower Theatre in Washington, D.C.. After the show opened, Wendt was interviewed by local film critic Arch Campbell for a piece on the NBC Washington affiliate WRC. Wendt was asked, "What should people do when they see you around town?" After hesitating for a moment, Wendt held his thumbs up and replied, "If their impulse is to buy me a beer, then by all means, follow that impulse." In Spring 2007, Wendt performed in 12 Angry Men in Los Angeles. Wendt appeared as an American GI in the 2007 Christmas Special episode of British sitcom The Green Green Grass.
George starred in the Broadway musical Hairspray as the character of Edna Turnblad until November 2008. He appeared with his former Cheers co-star John Ratzenberger as a talent scout on Last Comic Standing during Season 6. He briefly appeared as Santa Claus in A Colbert Christmas: The Greatest Gift of All!. He also appeared in the 2008 horror film Bryan Loves You directed by Seth Landau.
On October 1, 2009, Wendt appeared on The Colbert Report the day before the IOC announced which city will host the 2016 Summer Olympics. In their way of supporting Chicago's bid for the games, Wendt and Stephen Colbert humorously insulted the three other bidding cities, Rio de Janeiro, Madrid, and Tokyo, all while drinking Chicago's favorite Old Style Beer. In 2009, Wendt starred as Santa Claus in Santa Buddies and also had a small role in the film Opposite Day.
Wendt was scheduled to appear in a production of Hairspray, reprising his role as Edna Turnblad, from September 8 to October 9, 2010. at the Charlottetown Festival in Prince Edward Island, Canada, from September 8 to October 9, 2010. Wendt played Santa in Elf the Musical on Broadway. The show opened November 14, 2010 and ran through January 2, 2011. Wendt starred in a production of Hairspray as Edna Turnblad at Rainbow Stage in Winnipeg, Manitoba, Canada from August 2, 2011 to August 21, 2011. Wendt also guest-starred in the TV series Hot In Cleveland as Yoder, based on his character Norm in Cheers. His first of two scenes took place in an Amish bar, where everyone in the bar yelled "Yoder!," referencing what the cast of Cheers would yell whenever he walked in.
From November 6, 2013 to January 19, 2014 Wendt starred in Never Too Late, a comedy with his wife, Actress Bernadette Birkett, at New Theatre Restaurant in Overland Park, Kansas. In this play, Wendt plays a successful lumber yard owner who is king of his castle and whose life is going exactly the way he wants until his wife comes back from a Doctor appointment with some big news.
In 2015, Wendt starred opposite his former Second City co-star Tim Kazurinsky in Bruce Graham's new comedy Funnyman at Northlight Theatre. The same year, Wendt appeared in the TBS sitcom Clipped, which aired for one season.
Wendt starred in The Fabulous Lipitones at New Theatre Restaurant in Overland Park, Kansas from November 30, 2016 to February 12, 2017.
Wendt starred as Willy Loman in “Death of a Salesman” at St. Jacob's Country Playhouse in Waterloo, Ontario, Canada from October 18 to November 4, 2017. (https://www.draytonentertainment.com/death-of-a-salesman)
