Kelton was a young comedienne in A-list movies during the 1930s, often as the leading lady's wisecracking friend. She had a memorable turn in 1933 as dance hall singer "Trixie" in The Bowery alongside Wallace Beery, George Raft, Jackie Cooper and Fay Wray. Directed by Raoul Walsh, the film depicts Steve Brodie, the first man to supposedly jump off the Brooklyn Bridge and live to brag about it. Kelton sings to a rowdily appreciative crowd in an energetic dive, using a curious New York accent to good comedic effect, with Beery and Raft arguing over her attentions afterward.
As the witty young Minnie in Gregory LaCava's pre-Code comedy Bed of Roses (1933), she plays a bawdy prostitute (along with Constance Bennett) fond of getting admiring men helplessly drunk before robbing them, at least until getting caught and tossed back into jail. Kelton has all the best lines, surprisingly wicked and amusing observations that would never be allowed in an American film after the Hollywood Production Code was adopted. The movie remains realistic in terms of the interactions of the characters and features an early turn by Joel McCrea as the leading man, a small boat skipper who pulls Bennett from the river after she dives to escape capture. She played Mrs. Paroo in The Music Man.
Ironically, given her later blacklisting, Kelton's last movie for years was called Whispering Enemies (1939). Her next screen appearance was on television in The Honeymooners and other sketches on the Gleason show. Kelton's abrupt departure due to the blacklist was explained away as a result of "heart problems".
During the 1940s, she was a familiar radio voice on such programs as Easy Aces, It's Always Albert, The Stu Erwin Show and the 1941 soap opera We Are Always Young. In 1949, she did the voices of five different characters on radio's The Milton Berle Show. She was also a regular cast member of The Henry Morgan Show. In the early 1950s, she played the tart maid in the Monty Woolley vehicle, The Magnificent Montague.
Kelton was the original Alice Kramden in The Honeymooners comedy sketches on the DuMont Television Network's Cavalcade of Stars. These sketches formed the eventual basis for the 1955 CBS sitcom The Honeymooners. Jackie Gleason starred as her husband Ralph Kramden, and Art Carney as their upstairs neighbor Ed Norton. Elaine Stritch played Trixie, the burlesque dancer wife of Norton, for one sketch before being replaced by Joyce Randolph.
Kelton appeared in the original sketches, generally running about 10 to 20 minutes, shorter than the later one-season half-hour series and 1960s hour-long musical versions.
In the 1960s, Kelton was invited back to Gleason's CBS show to play Alice's mother in an episode of the hour-long musical version of The Honeymooners (also known as The Color Honeymooners), with Sheila MacRae as a fetching young Alice. By this time, the original age discrepancies were reversed, with Ralph married to a much younger Alice than himself.
In 1963 Kelton appeared on The Twilight Zone, playing the overbearing mother of Robert Duvall in the episode "Miniature."
In her last years, she was strongly identified with Spic and Span because of her TV commercials for that product.
Kelton made her Broadway debut at age 17 in Jerome Kern's Sunny. She played "Magnolia" and sang a song of the same name.
Years later, she was twice nominated for Tony Awards: in 1960, as Best Supporting or Featured Actress (Musical) for Frank Loesser's Greenwillow and as Best Supporting or Featured Actress (Dramatic) for Spofford (1967–68). However, her most memorable Broadway appearance was as the impatient Mrs. Paroo (the mother of Marian Paroo) in Meredith Willson's The Music Man(1957), which she reprised in the 1962 film adaptation, the role for which she is probably best remembered.
Pert Kelton was part owner of the Warner Kelton Hotel, built in the late 1920s, at 6326 Lexington Avenue, Los Angeles. The hotel catered to actors and musicians such as Cary Grant, Orry Kelly, and Rodgers and Hart. It had a small outdoor theatre at its rear, along with a wishing well that may have inspired the song "There's a Small Hotel," from the musical "On Your Toes" (1936). It also housed a speakeasy in the basement. A sign above the hotel entrance reads "Joyously Enter Here".
On October 30, 1968, Kelton died of heart disease at age 61.