Fleming was from New York City and went to school in Forest Hills, Queens. After starring in the Ziegfeld Follies productions on Broadway, she started appearing in movies. One of her earliest film roles was a starring role in Range Feud as Judy Walton, the love interest of John Wayne. Fleming combined her dancing and cinematic interests in the 1932 movie Million Dollar Legs, in which she played the daughter of W. C. Fields' character. As part of a publicity stunt for the film, her legs were insured for the eponymous million dollars.

Fleming was unhappy with Hollywood, stating in a 1995 interview that she found "nothing more boring than working on a movie... I hated it!". At a dinner party held in the home of Samuel Goldwyn, she was seated next to Harpo Marx and found him fascinating. Despite his silent persona in films, she found Marx to be "a warm, fun, darling man to talk to". She pursued him relentlessly, dating for four years and proposing marriage to him on three separate occasions before he accepted. She ended her Hollywood career when she married Marx on September 28, 1936. Fleming's wedding to Marx was revealed to the public when President of the United States Franklin D. Roosevelt sent the couple a telegram of congratulations in November. Marx had sent a thank you letter to Roosevelt in appreciation for a signed photograph of the President, in which Marx had stated that he was "in line for congratulations, too, having been married since September" in an unspecified "little town up North".

Harpo died at age 75 on September 28, 1964, their 28th wedding anniversary. Following his death, Fleming became more involved in local activities, including the local League of Women Voters. She became an advisory planning commissioner for Rancho Mirage, California, and headed an organization dedicated to preserving development on the fragile desert hillsides. She served a total of 18 years on the district board of education and ran and lost in a campaign for the California State Assembly. Honoring her contributions, a Golden Palm Star on the Palm Springs, California, Walk of Stars was dedicated to her in 2002.

In a 1981 decision later overruled by the United States Court of Appeals for the Second Circuit in a case brought by Fleming, federal judge william C. Conner ruled that the producers of A Day in Hollywood / A Night in the Ukraine had improperly used the Marx Brothers characters in their Broadway theatre production and that the publicity rights of the comedians, even after their deaths, overrode the First Amendment issues raised by the show's creators. In April 1980, Conner refused to issue a preliminary injunction and allowed Producer Alexander H. Cohen to open as planned.

Fleming outlived Marx by almost forty years during which she was an Artist and Activist in the Palm Springs area. She died at age 94 on December 22, 2002, of a heart attack at Eisenhower Medical Center in Rancho Mirage. She was survived by a daughter, three sons, five grandchildren; and two great-grandchildren.