She is best known for her performances on the comedy-variety show Rowan & Martin's Laugh-In from 1968 to 1973, for which she won a Golden Globe Award and received five Emmy nominations.

Her first job in show business was at 19, traveling with singer Rudy Vallee in a live musical and comedy act during her summer break from college; it allowed her to graduate with an Actors' Equity Association union card.

She moved to New York City after graduation and was hired immediately for a lead role in an off-Broadway musical revue, the first of 19 in which she performed around the East Coast.

She worked alongside other young performers just beginning their careers at the time, including Barbra Streisand, Joan Rivers, Dom DeLuise, Bernadette Peters, and Carol Burnett.

She performed as "Shakundala the Silent", a bumbling magician's assistant to her comedy partner Dom DeLuise, who played "Dominic the Great".

[citation needed] Among her recurring characters on Laugh-In were Flicker Farkle, youngest of the Farkle family; Busy-Buzzi, a Hedda Hopper-type Hollywood gossip columnist; Doris Swizzler, a cocktail-lounge habituée who always got smashed with husband Leonard (Dick Martin); and one of the Burbank Airlines Stewardesses, inconsiderate flight attendants.

Her most famous character was "spinster" Gladys Ormphby, clad in drab brown with her bun hairdo covered by a visible hairnet knotted in the middle of her forehead.

Buzzi was featured as Gladys in many of the Dean Martin Celebrity Roasts from the MGM Grand Hotel in Las Vegas, ranting about notable roastees including Muhammad Ali, Frank Sinatra, and Lucille Ball.

In each case, Gladys pugnaciously attacked the honoree with her purse, and she would also hit Martin when he made disparaging remarks about her looks and her romantic prospects.

Buzzi also guest-starred as Chloe, the wife of phone company worker Henry Beesmeyer (Marvin Kaplan) on Alice in 1981.

"[8] Buzzi was a guest star on many television series, including Donny & Marie, The Flip Wilson Show, The Dean Martin Music and Comedy Hour, the Dean Martin Roasts, The Carol Burnett Show, Tony Orlando and Dawn, The Monkees, Emergency!, and variety series hosted by Leslie Uggams and by Glen Campbell.

Ruthie ran Finders Keepers, which sold items previously owned by fairy tale and nursery rhyme characters.

[citation needed] Buzzi had a successful nightclub act across the United States, including at Las Vegas's Sahara and at the MGM Grand hotels.

[citation needed] She had featured roles in more than 20 films, including Chu Chu and the Philly Flash, Freaky Friday, The North Avenue Irregulars, The Apple Dumpling Gang Rides Again, The Villain, The Adventures of Elmo in Grouchland, and a number of westerns for the European market known as the Lucky Luke series in which she plays the mother of the Dalton Gang.